Bruno et al. Annals of Intensive Care (2022) 12:26 https://doi.org/10.1186/s13613-022-00996-9 RESEARCH Open Access The association of the Activities of Daily Living and the outcome of old intensive care patients suffering from COVID‑19 Raphael Romano Bruno1, Bernhard Wernly2,3, Hans Flaatten4, Jesper Fjølner5, Antonio Artigas6, Philipp Heinrich Baldia1, Stephan Binneboessel1, Bernardo Bollen Pinto7, Joerg C. Schefold8, Georg Wolff1, Malte Kelm1, Michael Beil9, Sigal Sviri9, Peter Vernon van Heerden9, Wojciech Szczeklik10, Muhammed Elhadi11, Michael Joannidis12, Sandra Oeyen13, Eumorfia Kondili14, Brian Marsh15, Jakob Wollborn16, Finn H. Andersen17,18, Rui Moreno19,20, Susannah Leaver21, Ariane Boumendil22, Dylan W. De Lange24, Bertrand Guidet22,23, Christian Jung1* and COVIP study group Abstract Purpose: Critically ill old intensive care unit (ICU) patients suffering from Sars-CoV-2 disease (COVID-19) are at increased risk for adverse outcomes. This post hoc analysis investigates the association of the Activities of Daily Living (ADL) with the outcome in this vulnerable patient group. Methods: The COVIP study is a prospective international observational study that recruited ICU patients ≥ 70 years admitted with COVID-19 (NCT04321265). Several parameters including ADL (ADL; 0 = disability, 6 = no disability), Clinical Frailty Scale (CFS), SOFA score, intensive care treatment, ICU- and 3-month survival were recorded. A mixed- effects Weibull proportional hazard regression analyses for 3-month mortality adjusted for multiple confounders. Results: This pre-specified analysis included 2359 patients with a documented ADL and CFS. Most patients evi- denced independence in their daily living before hospital admission (80% with ADL = 6). Patients with no frailty and no disability showed the lowest, patients with frailty (CFS ≥ 5) and disability (ADL < 6) the highest 3-month mortality (52 vs. 78%, p < 0.001). ADL was independently associated with 3-month mortality (ADL as a continuous variable: aHR 0.88 (95% CI 0.82–0.94, p < 0.001). Being “disable” resulted in a significant increased risk for 3-month mortality (aHR 1.53 (95% CI 1.19–1.97, p 0.001) even after adjustment for multiple confounders. Conclusion: Baseline Activities of Daily Living (ADL) on admission provides additional information for outcome pre- diction, although most critically ill old intensive care patients suffering from COVID-19 had no restriction in their ADL prior to ICU admission. Combining frailty and disability identifies a subgroup with particularly high mortality. Trial registration number: NCT04321265. *Correspondence: christian.jung@med.uni-duesseldorf.de 1 Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Moorenstraße 5, 40225 Duesseldorf, Germany Full list of author information is available at the end of the article © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. Bruno et al. Annals of Intensive Care (2022) 12:26 Page 2 of 11 Graphical Abstract Introduction its importance for outcome prediction with and with- Older patients admitted to an intensive care unit are at out Covid-19 [1, 2, 6, 8]. Apart from CFS, other instru- significantly increased risk for adverse outcome [1, 2]. ments have been proposed. The Israeli Position Paper, for Old patients make up the subgroup of intensive care example, named the Activities of Daily Living (ADL) as unit patients with the highest mortality [3]. However, the a candidate for the medical assessment tools that should chronological age is a worse parameter for the outcome be considered for assessing function during triage situ- prediction of critically ill older patients [4, 5]. This is par- ations [9]. ADL had been introduced in the early 1980s. ticularly true for SARS-CoV-2 and its disease COVID- It is a tool to evaluate individual independence in daily 19, which challenge intensive care units worldwide [6]. living. Initially, it was intended to assess the performance During the peaks of pandemic, the sheer volume of of older patients determining life expectancy [10]. The patients with COVID-19 has overwhelmed intensive scale includes routine tasks, which patients perform dur- care resources in many hospitals. In some countries, ing their daily routines, such as basic feeding, bathing, age cut-offs for ICU admission had been discussed [7], movement (transferring and getting out of bed), sphinc- but soon medical societies recommend other instru- ter control, and bathroom use. For non-COVID patients, ments for triage and outcome prediction. However, the it has been found that old patients requiring mechanical evidence for some components of the triage decision- ventilation, low ADL scores—meaning higher grades of making was relatively scarce. A well-established tool is dependence—were independently associated with worse the Clinical Frailty Scale (CFS) which assesses the func- outcome [11]. Currently, the value of ADL for outcome tioning of the old patient regarding fitness and frailty. prediction of severe COVID-19 and its sequelae remains Its association with ICU and 30-day mortality showed unclear. To address this lack of evidence, we performed Bruno et al. Annals of Intensive Care (2022) 12:26 Page 3 of 11 a post hoc analysis of the COVIP-Study (COVID-19 in renal replacement therapy. The eCRF also asked about very old intensive care patients). any limitation of life-sustaining treatment during the This multicentre study investigates the association of ICU stay. The eCRF and database ran on a secure server pre-existing disability regarding the Activities of Daily composed and stored in Aarhus University, Denmark. Living (ADL) with and without pre-existing frailty (CFS) on the one hand and the outcome on the other hand in a The activity of daily living, frailty, and comorbidities large prospectively recruited cohort of old ICU patients The Katz Activities of Daily Living (ADL) score assessed (≥ 70 years) with COVID-19. the patient’s independence in daily living before hospital admission. ADL is a commonly utilised graded instru- ment to evaluate disability and the level of dependence Methods in chronically ill or older patients. It assesses six pri- Design and settings mary and psychosocial functions: bathing, dressing, COVIP aimed to identify predictors for mortality in older going to the toilet, transferring, feeding, and continence. patients suffering from severe COVID-19. This multicen- Every patient receives 1 point for each independent and tre study was part of the Very old Intensive care Patients 0 for every dependent activity (6 = independent patient, (VIP) project and was endorsed by the European Soci- 0 = very dependent patient). Depending on the trial and ety of Intensive Care Medicine (ESICM) (www.​vipst​udy.​ context, the cut-off defining “disability” varies. ADL org). COVIP was registered on ClinicalTrials.gov (ID: could be obtained by the patient himself, by caregivers/ NCT04321265) and followed the European Union Gen- family, hospital records, or other sources. To charac- eral Data Privacy Regulation (GDPR) directive applied terise the cohort more precisely, we divided it into two in most participating countries. As in the previous VIP- groups: an ADL score of 6 was defined as “no disabil- studies [1, 2], national coordinators recruited the ICUs, ity”, < 6 as “disable” [12]. The Clinical Frailty Scale (CFS) coordinated national and local ethical permissions, and was evaluated as described previously [1, 2]. The respec- supervised patient recruitment at national level. For all tive visual and simple description for this assessment tool centres ethical approval was mandatory for study par- was used with permission [10, 13, 14] and distinguished ticipation. In most countries, informed consent was nine classes of frailty from very fit (CFS 1) to terminally obligatory for inclusion depending on local legal regula- ill (CFS 9). A CFS ≥ 5 was considered as “frailty”. The tions. This study used patient data from 151 ICUs from SOFA score was recorded on admission; it was calculated 26 independent countries, including European ICUs, and manually or using an online calculator. In the next step, the Asian, African, and Americas. patients were divided into three groups according to their CFS and ADL: Patients without frailty and without dis- Study population ability (CFS < 5, ADL 6), patients with either frailty or dis- Patients with proven (PCR diagnosed) COVID-19 aged ability CFS ≥ 5 or ADL < 6, and patients with both frailty 70 years or older who were admitted to an intensive care and disability (CFS ≥ 5 and ADL < 6). unit were recruited. The dataset for this subgroup analy- sis was extracted from the study database on the 15th of July 2021. Thus, the database included patients who were Statistical analysis admitted from the 19th of March 2020 to the 15th of July We did not perform a formal sample size calculation 2021. Data collection for each patient commenced at ICU prior to this purely observational study. The analysis admission. The admission day was defined as day one, plan was finalised prior to any analysis. The primary and all consecutive days were numbered sequentially exposure were disability (ADL) and frailty (CFS), the from the admission date. For this analysis, only patients primary outcome was 30-month survival, and the sec- with a documented CFS and ADL were included. ondary outcomes were overall survival up to discharge from ICU, survival 30 days after ICU admission, organ Data collection and storage support (vasoactive drugs, invasive mechanical ventila- All centres used a uniform online electronic case report tion, non-invasive ventilation, and renal replacement form (eCRF). As previously analysis, only patients with therapy) and treatment limitation. Continuous data a documented ADL were included. As previously, the points are expressed as median ± interquartile range. Sequential Organ Failure Assessment (SOFA) score on Differences between independent groups were calcu- admission was calculated either manually or using an lated using the Mann–Whitney U-test. Categorical online calculator in the eCRF [1, 2]. Furthermore, COVIP data are expressed as numbers (percentage). The Chi- assessed the need for non-invasive or invasive ventilation, square test was applied to calculate differences between prone positioning, tracheostomy, vasopressor use and groups. A mixed-effects Weibull proportional hazard Bruno et al. Annals of Intensive Care (2022) 12:26 Page 4 of 11 regression was performed using ADL as a categorical per country and the local COVID incidence on the day (ADL 6 or ADL ≥ 5 meaning a patient with independ- of ICU admission. We chose the independent variables ence in daily living) and continuous variable (ADL 0 based on differences in the baseline characteristics, to 6) and 3-month mortality (primary outcome). We previous reports, and our own clinical experience. The fitted models for the dependent variables with robust adjusted hazard ratios (HR) with respective 95% confi- standard errors. The regression analyses were con- dence intervals (95% CI) were calculated: HR describes ducted using only robust estimators of the standard the change in risk of death per each unit increase for errors and not in the sense of robustness against vio- continuous variables and for one specific category vs. lations of normality assumptions as for the robust a reference category for categorical variables. A HR > 1 methods (e.g., Mann–Whitney tests) used for the uni- suggests an increase in the risk of death, HR < 1 suggest variate analyses [15]. Three models was performed a decrease in the risk of death. All tests were two-sided, [16]. Model-2 added age, gender und SOFA. To adjust and a p-value of < 0.05 was considered statistically the effect for ICU capacities and COVID-19 incidence, significant. Since not all parameters were available model-3 additionally comprises ICU beds per 100.000 for all categories, patients had to be excluded for the Table 1 Baseline characteristics of patients with disability (ADL < 6) and without (ADL 6) No disability (ADL 6) Disability (ADL < 6) p-value N = 1884 N = 475 Male sex ([%], n) 74% (1,394) 58% (276) < 0.001 Age (years) 75 (4) 78 (5) < 0.001 SOFA 5 (3) 7 (4) < 0.001 CFS 3 (1) 5 (2) < 0.001 Diabetes mellitus ([%], n) 31% (589) 52% (246) < 0.001 CAD ([%], n) 20% (380) 34% (160) < 0.001 Chronic renal failure ([%], n) 12% (230) 29% (139) < 0.001 Arterial hypertension ([%], n) 64% (1,212) 77% (364) < 0.001 Pulmonary disease ([%], n) 21% (398) 32% (151) < 0.001 Chronic heart failure ([%], n) 12% (219) 28% (133) < 0.001 ADL Activities of Daily Living, CFS Clinical Frailty Scale, CAD coronary artery disease, SOFA Sequential Organ Failure Assessment; p-value comparing all groups. [Numbers do not add up to 100% due to missing values] Table 2 Baseline characteristics of patients without frailty (CFS < 5) and disability (ADL 6), patients with either disability (ADL < 6) or Frailty (CFS ≥ 5), or both frailty and disability Non-frailty (CFS < 5)/no Frailty (CFS ≥ 5) or disability Frailty and disability p-value disability (ADL 6) (ADL < 6) n = 1829 n = 260 n = 270 Male sex ([%], n) 73% (1342) 67% (173) 57% (155) < 0.001 Age (years) 75 (4) 77 (6) 78 (5) < 0.001 SOFA 5 (3) 6 (3) 8 (4) < 0.001 CFS 3 (1) 5 (1) 6 (1) < 0.001 Diabetes mellitus ([%], n) 31% (557) 48% (125) 57% (153) < 0.001 CAD ([%], n) 20% (358) 30% (78) 39% (104) < 0.001 Chronic renal failure ([%], n) 11% (206) 27% (71) 34% (92) < 0.001 Arterial hypertension ([%], n) 64% (1167) 75% (194) 80% (215) < 0.001 Pulmonary disease ([%], n) 21% (377) 29% (74) 36% (98) < 0.001 Chronic heart failure ([%], n) 11% (196) 29% (73) 31% (83) < 0.001 ADL Activities of Daily Living, CFS Clinical Frailty Scale, CAD coronary artery disease, SOFA Sequential Organ Failure Assessment, p-value comparing all groups. [Numbers do not add up to 100% due to missing values] Bruno et al. Annals of Intensive Care (2022) 12:26 Page 5 of 11 Table 3 Outcome and intensive care treatment of patients without frailty (CFS < 5) and disability (ADL 6), patients with either disability (ADL < 6) or frailty (CFS ≥ 5), or both frailty and disability Non-frailty (CFS < 5)/no Frailty (CFS ≥ 5) or Frailty and disability p-value disability (ADL 6) disability (ADL < 6) Invasive mechanical ventilation 76% (1388) 62% (162) 68% (183) < 0.001 Non-invasive mechanical ventilation 23% (414) 29% (75) 31% (84) 0.002 Tracheostomy 21% (376) 12% (31) 10% (28) < 0.001 Vasoactive drugs 72% (1312) 58% (149) 67% (178) < 0.001 RRT​ 14% (255) 16% (41) 23% (61) < 0.001 Life sustaining care withheld 30% (540) 42% (106) 31% (83) < 0.001 Life sustaining care withdrawn 20% (369) 21% (52) 16% (44) 0.32 ICU mortality 45% (810) 55% (140) 67% (180) < 0.001 30-day mortality 46% (848) 63% (162) 72% (195) < 0.001 3-month mortality 52% (945) 68% (176) 78% (210) < 0.001 ADL Activities of Daily Living, CFS Clinical Frailty Scale, RRT​ renal replacement therapy, p-value comparing all groups. [Numbers do not add up to 100% due to missing values] Table 4 Mixed-effects Weibull proportional hazard regression analyses for 3-month mortality (aHR (95% CI, p-value)) Model-1 Model-2 Model-3 ADL continuous 0.84 (0.80–0.89, p < 0.001) 0.91 (0.87–0.96, p 0.001) 0.88 (0.82–0.94, p < 0.001) ADL binary (ADL < 6) 1.83 (1.50–2.21, p < 0.001) 1.34 (1.09–1.65, p 0.006) 1.53 (1.19–1.97, p 0.001) ADL binary (ADL < 5) 1.75 (1.44–2.13, p < 0.001) 1.23 (0.99–1.52, p 0.060) 1.57 (1.21–2.03, p 0.001) Frailty or disability (ADL < 6 or 1.77 (1.39–2.25, p < 0.001) 1.51 (1.22–1.88, p < 0.001) 1.88 (1.47–2.40, p < 0.001) CFS ≥ 5) Frailty and disability 2.43 (1.87–3.16, p < 0.001) 1.58 (1.19–2.10, p 0.002) 1.94 (1.39–2.71, p < 0.001) aHR adjusted hazard ratio, ADL Activities of Daily Living, CFS Clinical Frailty Scale, ICU intensive care unit, SOFA Sequential Organ Failure Assessment Model-1: Individual ICU as random effect, and ADL/CFS as fixed effects Model-2: Model-1 plus SOFA, gender, age Model-3: Model-2 plus ICU beds per 100.000 per country and the local COVID-19 incidence on the day of ICU admission subgroup analyses. For this reason, not all patient num- Baseline characteristics of patients with disability bers add up to 100% (see Tables 1, 2, 3, and 4). Stata compared to patients without disability 16 was used for all statistical computations (StataCorp Patients without significant impairment in the Activi- LLC, 4905 Lakeway Drive, College Station, Brownsville, ties of Daily Living (ADL 6) were predominantly male Texas, USA). GraphPad Prism 5 (GraphPad Software, (74%, p < 0.001), younger (75 years (IQR 4) vs. 78 years San Diego, CA 92108, USA) was used for figures. (IQR 5), p < 0.001), less frail (CFS 3 (IQR 1) vs. 5 (IQR 2), p < 0.001) and significantly less affected by comorbidities Results (Table 2). In contrast, with increasing disability patients Study population were older, more frail and had significantly more comor- In total, this subgroup analysis included 2359 patients bidities. SOFA score on admission was significantly lower from the COVIP study with a documented ADL and in patients with high ADL (ADL 6: 5 (IQR 3); ADL < 6: 7 CFS (see Fig. 1). Most of the patients did not show any (IQR: 4), p < 0.001) (Fig. 3). dependence in their daily living prior to hospital admis- sion (80% ADL 6, Fig. 2A), although frailty in CFS was Intensive care treatment and outcome of patients distributed more heterogeneously (Fig. 2B), most patients with disability compared to patients without disability lived without severe frailty (81% CFS < 5, Fig. 2). During intensive care treatment, patients with pre-exist- ing disability received significantly less invasive mechani- cal ventilation (67 vs. 75%, p = 0.001), tracheostomy Bruno et al. Annals of Intensive Care (2022) 12:26 Page 6 of 11 Fig. 1 Consort diagram Fig. 3 Kaplan–Meier for patients with a disability (ADL < 6, red line) compared to patients without a disability (ADL 6, blue line) (3-month mortality, ± 95% CI). p < 0.001 log-rank test (12 vs. 20%, p < 0.001), vasoactive drugs (62 vs. 72%, p < 0.001), but more renal replacement therapies (19 vs. 14%, p = 0.006), and non-invasive ventilation (31 vs. 23%, p < 0.001). Limitations of life-sustaining therapy occurred significantly more often in patients without dis- ability. Patients with disability suffered from significantly increased crude ICU- (62 vs. 45%, p < 0.001), 30-day (66 vs. 47%, p < 0.001), and 3-month mortality (71 vs. 53%, p < 0.001, Figs. 4 and 5). Using an ADL of less than 5 as Fig. 2 A Distribution of documented ADL on admission (6 = no disability; 0 = fully dependend). B Distribution of CFS (1 = no frailty; cut-off resulted in similar outcomes (see Fig. 6). 9 = terminally frail) Bruno et al. Annals of Intensive Care (2022) 12:26 Page 7 of 11 Fig. 4 ICU-, 30-day and 3-month mortality [%] for patients with Fig. 6 Kaplan–Meier for patients with a disability (ADL < 5, red neither frailty (CFS ≤ 5) nor disability (ADL 6), frailty or disability, or line) compared to patients without a disability (ADL ≥ 5, blue line) frailty and disability. **p < 0.001 (3-month mortality, ± 95% CI). p < 0.001 log-rank test 5), p < 0.001) and had significantly more comorbidities (Additional file 1: Table S1). Therefore, with decreasing frailty patients were younger and had less comorbidities. Like patients without disability, SOFA score was lower in patients with a low frailty score (CFS < 5: 5 (IQR: 3); CFS ≥ 5: 7 (IQR: 4, p < 0.001). After admission to the ICU, invasive mechanical ventilation (66 vs. 75%, p < 0.001) and tracheostomy (11 vs. 20%, p < 0.001) occurred sig- nificantly more often in patients without pre-existing frailty. There was no difference regarding the use of vaso- active drugs. Patients with pre-existing frailty received significantly more non-invasive ventilation (30 vs. 23%, p = 0.005) and more renal replacement therapies (21 vs. 14%, p < 0.001). Frail patients evidenced a significantly Fig. 5 Kaplan–Meier for patients without a disability and frailty (ADL increased crude ICU- (65 vs. 45%, p < 0.001), 30-day (71 6 and CFS < 5, blue line) compared to patients with a disability or vs. 46%, p < 0.001), and 3-month mortality (77 vs. 52%, frailty (ADL < 6 or CFS ≥ 5), red line), and patients with disability and frailty (green line) (3-month mortality, ± 95% CI). p < 0.001 log-rank p < 0.001). test Comparison of patients without disability and frailty, with disability or frailty, and of patients with frailty In the mixed-effects Weibull proportional hazard and disability regression, ADL was associated with 3 months mortality When dividing into the three groups no disability/frailty, as a continuous variable (aHR 0.88 (0.82–0.94, p < 0.001)). either frailty or disability and frailty and disability, the This means that with rising ADL (= declining disability), results were similar: patients with frailty and disabil- the risk for mortality decreased. As binary variable, an ity were older (78 years (IQR 5), p < 0.001) and had sig- ADL < 6 (“disability”) was associated with an increased nificantly more comorbidities compared to the former 3 months mortality (aHR 1.53 (1.19–1.97, p 0.001), and groups (Table 2). Even though there was no difference an ADL of < 5 (aHR 1.57 (1.21–2.03, p 0.001), Table 3). in SOFA score between patients without disability and frailty and patients with disability and frailty (non-frailty, no disability: 5 (IQR: 3); frailty and disability: 8 (IQR: 4), Baseline characteristics of patients with frailty compared Table 2), the study shows individually that patients with to patients without frailty high independence in daily living evidenced lower scores Patients with high frailty (CFS ≥ 5) were as well pre- of organ failure on admission and patients without frailty dominantly male (61%, p < 0.001), older (78 years (IQR evidenced lower scores of organ failure on admission. Bruno et al. Annals of Intensive Care (2022) 12:26 Page 8 of 11 There were significant differences both in short- and dependence/disability and was significantly associated long-term outcome: combining ADL and CFS to three with nosocomial infection (p < 0.05) [22]. In a very small groups (no disability/frailty, either frailty or disability, cohort of 16 intensive care patients, pre-admission ADL frailty and disability) resulted into the following. was 6 (IQR 5–6) [23]. The two variables frailty and disability as well as either There is no commonly accepted cut-off for ADL that frailty or disability were significantly associated with distinguishes "dependence" from "independence". Gian- the 3-month mortality (Table 4): suffering from frailty nasi et al. defined every patient with an ADL below 6 as or disability, was an independent risk factor (aHR 1.88 "dependent". Their prospective cohort study included 249 (1.47–2.40, p < 0.001)) but the highest risk was found for patients aged 65 years or older who were admitted to the patients with both frailty and disability (aHR 1.94 (1.39– ICU and required mechanical ventilation for more than 2.71, p < 0.001)). Patients with no frailty and no disability 48 h. The logistic regression analysis with adjustment for evidenced a significantly lower mortality (ICU-mortal- APACHEII score and age revealed an independent asso- ity 45%, 30-day mortality 46%, 3-month mortality 52%, ciation of ADL with mortality (OR: 2.35, 95% CI: 1.16– p < 0.001), patients with frailty and disability the high- 4.75) [24]. Demesielle et al. used an ADL cut-off of 5 in est mortality (ICU-mortality 67%, 30-day mortality 72%, their prospective multicentric observational cohort study 3-month mortality 78%, p < 0.001, Table 3, Figs. 5 and with 501 patients aged 75 years or older who required 6). Patients who suffered either from frailty or disability mechanical ventilation. They found that an ADL ≤ 5 was were in-between (ICU-mortality 55%, 30-day mortality not associated with increased in-hospital mortality (OR 63%, 3-month mortality 68%, p < 0.001). Therefore, with 0.88; 95% CI 0.54–1.42, p = 0.598), but increased 1-year the detection of both ADL and CFS a subset of patients mortality (aOR 0.53, 95% CI 0.30–0.96, p = 0.038) [11]. with an almost 80% 3 months mortality can be identified. In 123 ICU patients with severe pneumonia, Sangla e al. defined three groups of dependence for the 1-year Discussion follow-up: ADL of 6, from 5 to 3, and below 3 [25]. Sch- The Activities of Daily Living before acute illness have been weikert et al. defined a cut-off below 6 as dependence proposed as a tool for outcome prediction in triage during in a prospective interventional intensive care study in the COVID-pandemic. The present study is based on the patients aged 18 years or older [26]. Langlet et al. used large international COVIP database and reveals that ADL an ADL score of 6 to define a full function, an ADL of 5 is an independent prognosticator for outcome in critically a low degree of impairment, an ADL 4–3 for moderate ill old patients admitted to the ICU and who suffer from impairment, and two or less for severe functional impair- COVID-19. However, most patients evidenced a high degree ment. Their study compared 26 patients with chronic of independence on admission, which might be interpreted obstructive pulmonary disease undergoing mechanical as consequence of triage. It is well known that pre-existing ventilation. In their study, the ADL score was a significant disability is a risk factor in intensive care patients, but the predictor of 6-month mortality [12]. VIP-2 used a cut-off crucial finding of our study is that combining of pre-existing of an ADL of less than 5 defining “disability” [1]. In the disability with pre-existing frailty identifies a subgroup with present study, there was no relevant difference between extraordinary high mortality. the ADL cut-offs 5 and 4 (for ADL ≤ 5, see Fig. 6). Historically, there are different approaches to assessing The timing of ADL use also differs between studies. the functional status of old patients before ICU admis- While many use the pre-acute condition as a reference, sion. Many studies in intensive care used functional other studies use the ADL score at the time of discharge assessments of survivors of critical illness with respira- from acute care. MacDonald et al. scored 42 patients who tory failure such as ADL [17–20]. There are insufficient were discharged after being treated with veno-venous data on what ADL scores should be considered "nor- extra-corporal life support for acute respiratory failure. mal" in a selected population of critically ill and old ICU They found high ADL scores, indicating high independ- patients. Level et al. conducted a prospective cohort ence and functionality in 62% of patients [27]. In a pro- study with 188 patients aged 75 years or older admitted spective, multicentre cohort study that recruited patients to the ICU. They found a median ADL of 4.2 ± 1.6 on who were admitted to the ICU with respiratory failure or admission. Furthermore, ADL on admission was inde- shock, a relevant dependence could be found in 23% of pendently predictive for one-year mortality [21]. Maziere the patients 12 months after discharge. Of note, in this et al. investigated a similar cohort with 223 critically ill, study, disability was defined as ADL < 6 [28]. old patients. In their investigation, ADL at admission In VIP-2, survivors had significantly higher ADL values was 3.8 ± 2.2. An ADL from 0 to 3 was defined as severe than non-survivors (6 (5–6) vs. 6 (3–6), p < 0.001); 27.7% Bruno et al. Annals of Intensive Care (2022) 12:26 Page 9 of 11 (962/3473) of the patients had an ADL ≤ 4; and 59.6% an admission. Combining pre-existing frailty with pre- ADL of 6 [1]. By contrast, in the present COVIP-study, existing disability identifies a subgroup that evidences only 16% (430/2692) patients had an ADL ≤ 4; and 84% extremely high mortality rates. Thus, the initial assess- had an ADL > 5 (2262/2692). However, it should be noted ment of ADL might offer an additional value for outcome that VIP-2 included patients aged 80 years and older, but prediction. COVIP included patients aged 70 years and older. In the pandemic of SARS-Cov-2, CFS provides valuable and reliable information for outcome prediction [6]. Com- Evidence before this study pared to CFS, the assessment of ADL might be more The value of Activities of Daily Living (ADL) could time-consuming [29] (compare Additional file 1: Table S2 be used for outcome prediction of critically ill elderly and Fig. S1, Additional file 2). patients. Limitations This is not the first study showing that pre-existing dis- Added value of this study ability is an independent risk factor for ICU outcome, This study with 2359 patients investigated the role of but it is the first investigating its value in a selected ADL in outcome prediction in severe cases of COVID- high-risk population of critically ill old patients suf- 19. The combination of ADL with frailty might provide fering from COVID-19. Furthermore, to our best additional prognostic information. knowledge, it is the first investigation that analyses the overlap between frailty and disability in this particularly Implications of all the available evidence vulnerable cohort. Our study has some methodologi- ADL offers additional information on intensive care cal limitations. For example, we did not have a control and 3-month mortality, although most patients evi- group of younger COVID-19 patients for comparison denced normal degrees of independence prior to ICU or a comparable age cohort of patients who were not or admission. The combination of an increased frailty could not be admitted to the ICU. In addition, COVIP (according to Clinical Frailty Scale) with reduced inde- does not capture information on pre-ICU care and tri- pendence (= increased disability) in the Activities of age. Thus, it might be hypothesised that during pan- Daily Living identifies a subgroup with mortality rates demic peaks patients with low ADL might not have up to 80%. been admitted to the ICU, and therefore do not appear in COVIP. Participating countries varied widely in their Supplementary Information care structure. This results in a large degree of het- The online version contains supplementary material available at https://​doi.​ erogeneity. The fact that CFS was recorded more fre- org/​10.​1186/​s13613-​022-​00996-9. quently overall than the ADL is probably also due to the study design of the COVIP group. COVIP, and its pre- Additional file 1: Table S1: Baseline characteristics of patients with Frailty (CFS ≥ 5) and without (CFS < 5). Table S2: Baseline characteristics decessors, focused on the role of CFS for outcome pre- of patients who survived 3 months after ICU admission. Figure S1. Katz diction. It may be argued that there is a strong overlap Index of Independence in Activities of Daily Living (ADL) from the COVIP- between frailty and disability, so that both scales meas- CRF, with permission. ure the same thing. However, it is argued that the mor- Additional file 2. COVIP study group. tality of the group who are both frail and dependent are significantly more at risk than patients who suffered Acknowledgements only either from frailty or disability. For this reason, Filiz Demirtas and Helene Mathilde Emilie Moecke helped with formatting, writing, and improving the manuscript. this study supports that both scales allow a comple- COVIP-study group (see Supplement 3, covip@med.uni-duesseldorf.de). mentary analysis of the patient. Last, the time frame of pre-existing ADL had not been defined in detail by the Authors’ contributions RRB, BW, GW and CJ analysed the data and wrote the first draft of the study. Thus, we do not know, if ADL reflects one month manuscript. HF and BG and DL and IS contributed to statistical analysis and or one year before acute COVID-19. improved the paper. PD and SB and BBP and JCS and MK and MB and MJ and SO and EK and BM and FHA and RM and FD and SL and AB gave guidance, contributed data, and improved the paper. All authors read and approved the final manuscript. Conclusion In critically ill old intensive care patients suffering from Funding Open Access funding enabled and organized by Projekt DEAL. This study was COVID-19, most patients evidenced high degrees of endorsed by the ESICM. Free support for running the electronic database and independence in Activities of Daily Living before ICU was granted from the dep. of Epidemiology, University of Aarhus, Denmark. Bruno et al. Annals of Intensive Care (2022) 12:26 Page 10 of 11 18 The support of the study in France by a grant from Fondation Assistance Pub- Department of Circulation and Medical Imaging, Norwegian University lique-Hôpitaux de Paris pour la recherche is greatly appreciated. In Norway, of Science and Technology, Trondheim, Norway. 19 Hospital de São José, Centro the study was supported by a grant from the Health Region West. In addition, Hospitalar Universitário de Lisboa Central, Faculdade de Ciências Médicas de the study was supported by a grant from the European Open Science Cloud Lisboa, Nova Médical School, Lisbon, Portugal. 20 Universidade da Beira Interior, (EOSC). EOSCsecretariat.eu has received funding from the European Union’s Covilhã, Portugal. 21 General Intensive Care, St George´S University Hospitals Horizon Programme call H2020-INFRAEOSC-05-2018-2019, grant agreement NHS Foundation Trust, London, UK. 22 Sorbonne Universités, UPMC Univ Paris number 831644. This work was supported by the Collaborative Research 06, INSERM, UMR_S 1136, Institut Pierre Louis d’Epidémiologie et de Santé Center SFB 1116 (German Research Foundation, DFG) and by the Forschun- Publique, Equipe: épidémiologie hospitalière qualité et organisation des soins, gskommission of the Medical Faculty of the Heinrich-Heine-University 75012 Paris, France. 23 Assistance Publique ‑ Hôpitaux de Paris, Hôpital Saint- Düsseldorf and No. 2020–21 to RRB for a Clinician Scientist Track. No (industry) Antoine, Service de réanimation médicale, 75012 Paris, France. 24 Department sponsorship has been received for this investigator-initiated study. of Intensive Care Medicine, University Medical Center, University Utrecht, Utrecht, the Netherlands. Availability of data and materials Individual participant data that underlie the results reported in this article are Received: 2 November 2021 Accepted: 15 February 2022 available to investigators whose proposed use of the data has been approved by the COVIP steering committee. The anonymised data can be requested from the authors if required. References Declarations 1. Guidet B, de Lange DW, Boumendil A, et al. The contribution of frailty, cognition, activity of daily life and comorbidities on outcome in acutely Ethics approval and consent to participate admitted patients over 80 years in European ICUs: the VIP2 study. Inten- The primary competent ethics committee was the Ethics Committee of the sive Care Med. 2020;46(1):57–69. University of Duesseldorf, Germany. Institutional research ethic board approval 2. Flaatten H, De Lange DW, Morandi A, et al. 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