Risk Factors for the Impairment of Ambulation in Older People Hospitalized...

[Full title: Risk Factors for the Impairment of Ambulation in Older People Hospitalized with COVID-19: A Retrospective Cohort Study]

Citation: Silva, E.C.G.e.; Schmitt, A.C.B.; de Godoy, C.G.; de Oliveira, D.B.; Tanaka, C.; Toufen, C., Jr.; de Carvalho, C.R.R.; Carvalho, C.R.F.; Fu, C.; Hill, K.D.; et al. Risk Factors for the Impairment of Ambulation in Older People Hospitalized with COVID-19: A Retrospective Cohort Study Int. J. Environ. Res. Public Health 2023 , 20 , 7057. https:// doi.org/10.3390/ijerph 20227057 Academic Editor: Jean Woo Received: 11 October 2023 Revised: 4 November 2023 Accepted: 9 November 2023 Published: 13 November 2023 Copyright: © 2023 by the authors Licensee MDPI, Basel, Switzerland This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/) International Journal of Environmental Research and Public Health Article Risk Factors for the Impairment of Ambulation in Older People Hospitalized with COVID-19: A Retrospective Cohort Study Erika Christina Gouveia e Silva 1, * , Ana Carolina Basso Schmitt 1 , Caroline Gil de Godoy 1 , Danielle Brancolini de Oliveira 1 , Clarice Tanaka 1 , Carlos Toufen, Jr. 2 , Carlos Roberto Ribeiro de Carvalho 2 , Celso R. F. Carvalho 1 , Carolina Fu 1 , Keith D. Hill 3 and Jos é Eduardo Pompeu 1 1 Department of Physical Therapy, Speech and Occupational Therapy, School of Medicine—University of Sao Paulo, Brazil. R. Cipotanea, 51-Vila Butanta, S ã o Paulo 05360-160, Brazil; carolinaschmitt@usp.br (A.C.B.S.); caroline.gil@usp.br (C.G.d.G.); danibrancolini@usp.br (D.B.d.O.); cltanaka@usp.br (C.T.); cscarval@usp.br (C.R.F.C.); carolfu@usp.br (C.F.); j.e.pompeu@usp.br (J.E.P.) 2 Division of Pulmonology, Heart Institute (InCor), School of Medicine—University of Sao Paulo, Brazil. Av. Dr. Eneas Carvalho de Aguiar, 44-Cerqueira Cesar, S ã o Paulo 05403-900, Brazil; carlos.toufen@hc.fm.usp.br (C.T.J.); carlos.carvalho@hc.fm.usp.br (C.R.R.d.C.) 3 Rehabilitation Ageing and Independent Living (RAIL) Research Centre, Monash University, Melbourne, VIC 3199, Australia; keith.hill@monash.edu * Correspondence: erikacgc@usp.br Abstract: (1) Background: Some older people hospitalized with COVID-19 have experienced reduced ambulation capacity. However, the prevalence of the impairment of ambulation capacity still needs to be established. Objective: To estimate the prevalence of, and identify the risk factors associated with, the impairment of ambulation capacity at the point of hospital discharge for older people with COVID-19. (2) Methods: A retrospective cohort study. Included are those with an age > 60 years, of either sex, hospitalized due to COVID-19. Clinical data was collected from patients’ medical records Ambulation capacity prior to COVID-19 infection was assessed through the patients’ reports from their relatives. Multiple logistic regressions were performed to identify the risk factors associated with the impairment of ambulation at hospital discharge. (3) Results: Data for 429 older people hospitalized with COVID-19 were randomly collected from the medical records. Among the 56.4% who were discharged, 57.9% had reduced ambulation capacity. Factors associated with reduced ambulation capacity at discharge were a hospital stay longer than 20 days (Odds Ratio (OR): 3.5) and dependent ambulation capacity prior to COVID-19 (Odds Ratio (OR): 11.3). (4) Conclusion: More than half of the older people who survived following hospitalization due to COVID-19 had reduced ambulation capacity at hospital discharge. Impaired ambulation prior to the infection and a longer hospital stay were risks factors for reduced ambulation capacity Keywords: COVID-19; functional status; hospitalization; older people 1. Introduction Older people are more vulnerable to the adverse effects of hospitalization [ 1 ], including the impairment of functional capacity [ 2 ]. The greatest vulnerability is associated with the decline of several bodily systems and lower functional reserves due to aging [ 3 – 5 ], in addition to the reduced response to stressful stimuli [ 3 , 4 ]. Therefore, older people are more susceptible to immobility, sepsis, and hypoxemia [ 6 ]. Thus, hospital admissions can impair various functions of older people, including ambulation capacity [ 2 ]. Worldwide, there have been more than 771,154,224 confirmed cases of COVID-19, and more than 6,960,783 deaths caused by the disease [ 7 ]. The highest prevalence of severe cases was found in older people hospitalized with previous comorbidities (such as obesity, arterial hypertension, and diabetes) [ 8 – 13 ]. Treatment of severe COVID-19 requires long periods of hospitalization and bed rest [ 14 , 15 ]. Several studies have shown the negative impact of Int. J. Environ. Res. Public Health 2023 , 20 , 7057. https://doi.org/10.3390/ijerph 20227057 https://www.mdpi.com/journal/ijerph

Int. J. Environ. Res. Public Health 2023 , 20 , 7057 2 of 11 long hospital stays and immobility on the functional capacity of older people [ 12 , 16 – 19 ]. Thus, the tissue damage in multiple systems directly caused by the cellular invasion of SARS-CoV-2 [ 9 ], the intense systemic inflammatory response [ 8 ], and the adverse effects of hospitalization can cause a greater functional impact on older people [ 11 ]. Muscle inactivity and intensive care interventions, including mechanical ventilation, neuromuscular blocking agents [ 20 ], and prone positioning [ 21 ] can decrease muscle strength, joint mobility, and respiratory capacity [ 20 – 22 ], especially in older people [ 19 ]. These structural and functional consequences in critically ill patients can persist even after hospital discharge, and are known as post-intensive care syndromes [ 8 ]. They can trigger impairments in the performance of daily activities, negatively affect functionality [ 23 , 24 ], autonomy, and independence, and increase the risk of mortality [ 25 , 26 ] The longer the stay in the intensive care unit, the greater the risk of physical, cognitive, and emotional problems [ 27 ]. Approximately 25–45% of critically ill patients exhibit neuromuscular complications during and after intensive care, including symmetrical flaccid limb paralysis resulting from systemic inflammatory responses [ 28 ], which is associated with the use of steroid medication that can cause significant adverse effects, including immune dysfunction and sarcopenia [ 16 ]. Studies show that approximately 65% of older people hospitalized due to COVID-19 suffer a loss of mobility [ 16 , 19 ]. Still, the clinical and sociodemographic factors associated with functional decline and the prevalence of the impairment of ambulation capacity at hospital discharge have not yet been established Thus, the objectives of this study were to estimate the prevalence and identify the factors associated with the worsening of ambulation capacity at hospital discharge in older people admitted with COVID-19 2. Materials and Methods This retrospective study was performed at a referral public hospital for COVID-19 in Sao Paulo, Brazil, and was approved by the local ethics committee (number 4.052.246) Data were collected from a random sample of the medical records and managed using Research Electronic Data Capture (REDCap), which is a secure environment to store highly sensitive information. The inclusion criteria were older people aged 60 years or more [ 29 ]; both sexes; and hospitalized with a diagnosis of COVID-19 during the period from 1 April 2020 to 30 November 2020 (corresponding to the 1 st wave), or from 1 January 2021 to 31 May 2021 (2 nd wave). Cases with missing or dubious information in the medical records were excluded Sociodemographic data (age, sex, and race) and habits (tobacco and alcohol use) were processed. The clinical data consisted of the current COVID-19 wave at the point of admission (1 st or 2 nd); hospital outcome (discharge or death); comorbidities (immunosuppression, hematological, neurological, pulmonary, cardiovascular, renal, hepatic, systemic arterial hypertension, diabetes mellitus, obesity, and dyslipidemia); length of hospital stay and intensive care unit stay; and use of mechanical ventilation. The main outcome was the ambulation capacity before COVID-19 and at the point of hospital discharge. Patients’ ambulation capacity is evaluated and registered in their medical records by the physiotherapy team as a routine. Especially for this study, ambulation capacity prior to COVID-19 infection was assessed through the patients’ medical records Ambulation capacity classifications were adapted from Mehrholz et al. [ 30 ]. In order to decrease the number of categories, we grouped the following classifications: i Independent ambulator: Individual can ambulate independently on flat or uneven surfaces, stairs, and uneven slopes. This classification includes the categories “independent ambulator only on a flat surface” and “independent ambulator” ii Dependent ambulator: Individual requires manual contact with, at most, one person while ambulating on level surfaces in order to prevent falls; manual contact consists of continuous or intermittent touch to aid balance or coordination. This classification

Int. J. Environ. Res. Public Health 2023 , 20 , 7057 3 of 11 includes the categories “level III physical assistance-dependent ambulator” and “level I physical assistance-dependent ambulator and supervision-dependent ambulator” iii Nonfunctional ambulator: Requires maximum help, with the need for assistive technology Ambulation capacities at the point of hospital discharge were divided into two groups, according to their evolution: (a) “the same” (ambulation capacity did not change during hospitalization); and (b) “worse” (an independent ambulator prior to COVID-19 became a dependent or non-functional ambulator, or a dependent ambulator prior to COVID-19 became a non-functional ambulator at hospital discharge) The majority of patients with moderate or severe COVID-19 received corticosteroids, supplementary oxygen, and anti-thrombotic drugs [ 31 ], as well as rehabilitation with an early mobilization protocol [ 32 ]. Data Analysis Statistical analysis was performed using Stata 16 (StataCorp, College Station, TX, USA). Data distribution was analyzed through the Shapiro–Wilk statistic. Data did not follow a normal distribution, and thus, median and interquartile ranges were used for the continuous variables. Frequency (number and percentage) was presented for the nominal variables. The prevalence of the impairment of ambulation capacity at hospital discharge was estimated using a confidence interval. Sociodemographic and clinical characteristics were presented according to the ambulation capacity classification before COVID-19. The chi-squared test was used to verify the association between ambulation capacity before COVID-19 and in-hospital death, as well as the ambulation capacity evolution (the same or worse) at hospital discharge Bivariate logistic regression analysis was calculated for each independent variable with the impairment of ambulation capacity at hospital discharge. For the multivariate regression model, sociodemographic and clinical variables with p < 0.20 were included, and a correlation matrix was performed on one of the pair of highly correlated variables for the multivariate regression (length of hospital stay and length of intensive care unit stay). Finally, a multivariate regression model—adjusted for sex, race, tobacco use, obesity, dyslipidemia, and neurological diseases—was built to identify possible predictors for reduced ambulation capacity at hospital discharge. We adopted a significance level of 0.05 3. Results 3.1. Older People Hospitalized with COVID-19 Data from 429 older people hospitalized with COVID-19 were randomly collected from the medical records. The mean age of the older people included in this study was 68 (63–74) years, most were male (60.1%, n = 258), 32.0% ( n = 136) were brown, and 33.6% ( n = 143) were black. Before COVID-19 infection, 67.4% ( n = 289) of the older people were classified as independent ambulators, 15.8% ( n = 68) as dependent ambulators, and 16.8% ( n = 72) as non-functional ambulators In-hospital death occurred in 187 patients (43.6%). Patients who died during hospitalization had reduced ambulation capacity prior to COVID-19 (OR: 2.6; CI 95%: 1.7–4.9; p < 0.001) Among the 242 (56.4%) who were discharged, 42.1% ( n = 102) maintained the same level of ambulation as before COVID-19, and 57.9% ( n = 140) suffered reduced ambulation capacity (Flowchart 1). Hence, the prevalence of the impairment of ambulation capacity at hospital discharge was 57.9% (CI 95%: 51.4–64.1%) Age, race, tobacco use, neurological disease, use of invasive mechanical ventilation, in-hospital death, and current pandemic wave had an association with the classification of ambulation capacity prior to COVID-19 (Table 1 ).

Int. J. Environ. Res. Public Health 2023 , 20 , 7057 4 of 11 Table 1. Sociodemographic and clinical characteristics of the older people according to their functionality during the pre-admission assessment Sociodemographic and Clinical Characteristics Ability to Walk before Hospital Admission Independent Ambulator n = 289 (67.4%) Dependent Ambulator n = 68 (15.8%) Non-Functional Ambulator n = 72 (16.8%) Total n = 429 (100%) p ( χ 2 ) Age (years) 60–69 172 (69.9) 32 (13.0) 42 (17.1) 246 0.046 70–79 95 (68.8) 24 (17.4) 19 (13.8) 138 80 or older 22 (48.9) 12 (26.7) 11 (24.4) 45 Sex Female 113 (66.1) 27 (15.8) 31 (18.1) 171 0.828 Male 176 (66.2) 41 (15.9) 41 (15.9) 258 Race White 91 (52.3) 20 (13.7) 35 (24.0) 146 0.015 Brown 88 (64.7) 26 (19.1) 22 (16.2) 139 Black 108 (75.5) 21 (14.7) 14 (9.8) 143 Habits Tobacco 62 (67.5) 12 (15.2) 5 (6.3) 79 0.016 Alcoholic Beverage 8 (72.7) 2 (18.2) 1 (9.1) 11 0.782 Comorbidity Immunosuppression 30 (69.8) 9 (20.9) 4 (9.3) 43 0.299 Hematologic 3 (75.0) 1 (25.0) - 4 0.629 Neurologic 10 (41.7) 8 (33.3) 6 (25.0) 24 0.015 Pulmonary 20 (65.3) 5 (17.9) 5 (16.8) 30 0.992 Cardiovascular 62 (63.26) 17 (17.35) 16 (19.39) 95 0.818 Renal 8 (80.0) 2 (20.0) - 10 0.355 Hepatic 4 (80.0) 1 (20.0) - 5 0.599 Systemic Arterial Hypertension 153 (67.7) 40 (17.7) 33 (14.6) 226 0.302 Diabetes Mellitus 111 (70.3) 29 (18.3) 18 (11.4) 158 0.060 Obesity 49 (68.1) 15 (20.8) 8 (11.1) 72 0.221 Dyslipidemia 37 (77.1) 6 (12.5) 5 (10.4) 48 0.190 Hospitalization (>20 days) 118 (66.3) 36 (22.2) 24 (13.5) 178 0.059 Intensive care unit (>11 days) 135 (65.2) 38 (18.4) 34 (16.4) 207 0.332 Invasive mechanical ventilation 265 (65.59) 57 (14.11) 82 (20.30) 404 0.001 In-hospital death 106 (64.17) 31 (13.37) 50 (22.46) 187 0.684 <0.001 COVID-19 wave 1 st 107 (59.1) 22 (12.2) 52 (28.7) 181 2 nd 182 (73.4) 46 (18.5) 20 (8.1) 248 <0.001 Abbreviation: χ 2 = chi square. In bold, p-values that present a statistical difference 3.2. Ambulation Capacity at Hospital Discharge Table 2 shows that 105 (24.5%) individuals classified as independent and 35 (8.2%) individuals classified as dependent ambulators prior to COVID-19 had reduced ambulation capacity at hospital discharge. There was a significant difference between the level of ambulation capacity before COVID-19 and at hospital discharge ( χ 2 = 50.69, df = 6, p < 0.001), as shown in Table 2 below. In-hospital deaths of independent ambulators, dependent ambulators, and non-functional ambulators were 36.7% ( n = 106), 45.6% ( n = 31), and 69.4% ( n = 50), respectively. The proportions of reduced ambulation capacity for the independent ambulators and dependent ambulators were 36.3% ( n = 105) and 51.5% ( n = 35), respectively. Non-functional ambulators did not experience any change in their ambulation capacity at hospital discharge Table 3 shows the demographic and clinical characteristics of the older people who were discharged from the hospital (n = 242). The median age of the survivors was 67 years (63–73 interquartile range), and 52.9% ( n = 128) were male. Most of the older people (57.9%, 95%CI: 51.4–64.1%) had a reduced ambulation capacity at hospital discharge. Table 3 also presents the distribution and bivariate regression of demographic and clinical characteristics related to the ambulation capacity change at hospital discharge. The factors associated with reduced ambulation capacity were male sex; brown or black race; neurological disease; dyslipidemia; obesity; length of hospital stay longer than 20 days; intensive care stay longer

Int. J. Environ. Res. Public Health 2023 , 20 , 7057 5 of 11 than 11 days; being a dependent or non-functional ambulator prior to COVID-19; and hospitalization during the 2 nd wave Table 2. Ambulation capacity before COVID-19, in-hospital death, and reduced ambulation capacity at hospital discharge Ability to Walk before Hospitalization In-Hospital Death n = 187 (43.6%) At Hospital Discharge n = 252 (57.4%) Total Same Ambulation Capacity n = 102 (23.81%) Worse Ambulation Capacity n = 140 (32.6%) n = 429 p Independent Ambulator (n = 289) 106 (24.7) 78 (18.2) 105 (24.5) 289 (67.4) <0.001 χ 2 Dependent Ambulator ( n = 68) 31 (7.2) 2 (0.5) 35 (8.2) 68 (15.9) Non-Functional Ambulator ( n = 72) 50 (11.7) 22 (5.1) -- 72 (16.8) Abbreviation: χ 2 = chi square. In bold, p-values that present a statistical difference Table 3. Distribution and bivariate regression for the ambulation capacity change at hospital discharge ( n = 242) Demographic and Clinical Characteristics Ambulation Capacity at Hospital Discharge Same n = 102 (42.1%) Worse n = 140 (57.9%) OR (CI 95%) p Age (years) 60–69 61 (42.9) 81 (57.1) Ref 70–79 35 (44.3) 44 (55.7) 1.0 (0.5–1.6) 0.847 80 years or older 6 (28.6) 15 (71.4) 1.8 (0.7–5.1) 0.217 Sex Female 57 (50.0) 57 (50.0) Ref Male 45 (35.2) 83 (64.8) 1.8 (1.1–3.1) 0.020 Color/Race White 47 (58.8) 33 (41.2) Ref Brown 27 (33.3) 54 (66.7) 2.8 (1.5–5.4) 0.001 Black 27 (34.6) 51 (65.4) 2.7 (1.4–5.1) 0.003 Habits Tobacco 13 (30.9) 29 (69.1) 1.7 (0.8–3.5) 0.124 Alcoholic beverage – 4 (100.0) --- --- Comorbidities Immunosuppression 9 (36.0) 16 (64.0) 1.3 (0.6–3.1) 0.512 Hematologic 1 (50.0) 1 (50.0) 0.7 (0.1–11.7) 0.822 Neurologic 3 (721.4) 11 (78.6) 2.8 (0.7–10.3) 0.120 Pulmonary 9 (56.3) 7 (43.7) 0.5 (0.2–1.5) 0.243 Cardiovascular 29 (46.0) 34 (54.0) 0.8 (0.4–1.4) 0.468 Renal 2 (33.3) 4 (66.7) 1.5 (0.3–8.2) 0.660 Hepatic 1 (33.3) 2 (66.7) 1.4 (0.1–16.3) 0.757 Systemic Arterial Hypertension 62 (44.9) 76 (55.1) 0.7 (0.4–1.3) 0.314 Diabetes Mellitus 42 (42.4) 57 (57.6) 1.0 (0.6–1.6) 0.942 Obesity 12 (30.8) 27 (69.2) 1.8 (0.8–3.7) 0.119 Dyslipidemia 4 (19.1) 17 (80.9) 3.4 (1.1–10.4) 0.033 Hospitalization (>20 days) 32 (28.3) 81 (71.7) 2.9 (1.7–5.0) <0.001 Intensive care unit (>11 days) 29 (19.0) 71 (71.0) 1.9 (1.1–3.4) 0.027 Invasive mechanical ventilation 91 (43.1) 120 (56.9) 0.6 (0.3–1.5) 0.211 Ambulation capacity before COVID-19 Independent Ambulator 78 (42.6) 105 (57.4) Ref Dependent Ambulator 2 (5.4) 35 (94.6) 13.0 (3.0–55.6) 0.001 2 nd wave 28 (26.4) 106 (73.6) 5.2 (3.0–9.1) <0.001 Abbreviations: Ref = reference; OR = odds ratio; CI = 95% confidence interval; p = probability of significance. In bold, odds ratio (OR) and p -values that present a statistical difference.

Int. J. Environ. Res. Public Health 2023 , 20 , 7057 6 of 11 Table 4 shows the predictors for reduced ambulation capacity at hospital discharge The worsening of ambulation capacity was independent of sex, race, tobacco use, obesity, dyslipidemia, and neurological diseases, but was associated with hospital stays longer than 20 days (OR: 3.5; CI 95%: 1.7–7.3; p = 0.001), being a dependent ambulator before COVID-19 (OR: 11.3; CI 95%: 1.4–52.7; p = 0.002), and hospitalization during the 2 nd wave (OR: 4.8; CI 95%: 2.1–11.1; p < 0.001) Table 4. Logistic regression adjusted for the ambulation capacity evolution at hospital discharge ( n = 214) Demographic and Clinical Characteristics Ambulation Capacity at Hospital Discharge OR (CI 95% ) p Sex Male 1.7 (0.9–3.6) 0.114 Color/Race White Ref Brown 1.7 (0.7–4.4) 0.203 Black 1.1 (0.4–2.7) 0.925 Tobacco Use 0.7 (0.3–1.9) 0.603 Obesity 1.2 (0.4–3.4) 0.770 Dyslipidemia 1.3 (0.3–5.6) 0.741 Neurological Diseases 3.8 (0.3–46.9) 0.293 Hospitalization > 20 days 3.5 (1.7–7.3) 0.001 Ambulation capacity before hospital admission Independent Ambulator Ref Dependent Ambulator 11.3 (1.4–52.7) 0.002 2 nd wave 4.8 (2.1–11.1) <0.001 Abbreviations: OR = odds ratio; CI = 95% confidence interval. In bold, odds ratio (OR) and p -values that present a statistical difference 4. Discussion The prevalence of the decreased ambulation capacity of older adults hospitalized due to severe COVID-19 was 57.9%. The factors associated with the worsening in ambulation capacity at hospital discharge were hospital stays higher than 20 days; decreased ambulation capacity before COVID-19; and hospitalization during the 2 nd wave of the pandemic Our findings concerning the worsening in ambulation capacity are consistent with studies in which acute post-COVID-19 patients presented with alterations in musculoskeletal and cardiorespiratory function [ 27 , 33 ]. Welch et al. [ 14 ] point out that a decline in muscle trophism and function may be common in patients with COVID-19. However, our in-hospital mortality (43.6%) was higher than previously reported (20% to 31%) [ 8 , 19 , 34 ]. This finding may be related to our data collection site, which was a referral hospital for severe and moderate cases of COVID-19, where only patients with significant clinical worsening were transferred; these patients often required mechanical ventilation Our results showed that older adults with a hospital stay longer than 20 days presented a higher chance of suffering worsening in their ambulation capacity. In our study, the older adults stayed longer in the hospital (median 17 days) than in other studies (with a median hospital stay of 12 days) [ 10 , 13 ]. In a study that compared muscle strength and mobility between COVID-19 and non-COVID-19 patients, the results showed that muscle strength and mobility at ICU discharge are associated with the length of stay during COVID-19 infection [ 35 ]. Indeed, higher serum concentrations of inflammatory cytokines are seen in patients with COVID-19 who require intensive care [ 14 , 36 ] and stay longer in the hospital. This has negative consequences on muscle protein synthesis, resulting in a state of anabolic resistance, which requires a higher protein intake to stimulate muscle protein synthesis [ 14 , 27 ]. Worse ambulation capacity prior to COVID-19 (OR: 11.3) was also a predictor of reduced function at discharge. Our results corroborate a study that followed the functional

Int. J. Environ. Res. Public Health 2023 , 20 , 7057 7 of 11 trajectory of older adults among the people who had a mild to moderate disability before admission to the intensive care unit. In this study, 39.5% developed a severe disability, and of those who had a severe disability prior to their stay in the intensive care unit, one-third had an intra-hospital death [ 32 , 37 ]. In our study, it was not possible to verify the treatment intensities that each group received; however, Stripari et al. [ 38 ] analyzed the functional recovery of three groups of critically ill COVID-19 survivors following their hospital stay, with the application of the early mobilization protocol. Their results show that functionally independent patients who preserved their functional status during hospitalization recovered functionality (44%); other patients showed dependence at ICU discharge, but recovered their independence by hospital discharge (33.2%); and some functionally dependent patients who were dependent at ICU discharge had not recovered their functional status at hospital discharge (22.8%) This suggests that age and time spent on patient mobilization out of bed were independent factors associated with becoming physically dependent after their ICU stay Our results showed that older adults hospitalized during the 2 nd wave suffered a greater worsening in ambulation capacity than those hospitalized during the 1 st wave (OR: 4.8). We speculate that this finding could be related to the fact that there was a greater number of dependent and non-functional ambulators requiring hospitalization in this period, because of the 1 st wave. According to a study conducted by Moura et al. [ 39 ], the analysis of the 1 st and 2 nd waves in Brazil showed that there was a swift increase in the rate of cases and deaths in the 2 nd wave, and despite social distancing measures being required, they were not respected. Inevitably, the contamination rate was higher, which may explain the occurrence of more individuals with worse ambulation capacity prior to the 2 nd wave of COVID-19 Therefore, older adults with a lower ambulation capacity prior to COVID-19 had a worse ambulation prognosis at hospital discharge, as well as a higher prevalence of death. A longer hospitalization period can cause functional losses, especially in older adults with comorbidities and the need for sedation [ 19 , 40 ]; another study showed that frailty and age over 80 years were the main factors associated with functional decline after hospital discharge, due to chronic obstructive pulmonary disease [ 3 ]. According to Stam et al. [ 41 ], post-intensive care effects could be the next public health crisis to occur, as at least 20% of patients with COVID-19 require supportive care in intensive care units, and approximately 50% of all patients at different ages tend to develop post-intensive care syndrome It is known that older adults have exacerbated responses to SARS-CoV-2 infection, including muscle damage related to the intensification of myokine (muscle cytokine) production, resulting in an increased viral invasion of the peripheral and musculoskeletal nervous system and a heightened muscle inflammatory process, which causes symptoms such as fatigue, weakness, muscle atrophy, and myalgia [ 42 ]. Individuals hospitalized due to COVID-19 who were in critical condition are likely to be at greater risk of developing post-COVID syndrome [ 39 ], with the persistence of several signs and symptoms—such as chronic pain—that can further affect the recovery process and, thus, require a longer rehabilitation time [ 22 , 27 ]. In our opinion, direct effects from COVID-19 infection and indirect effects due to hospitalization and drug treatment, mainly corticosteroids, can negatively impact muscle mass and strength, which would explain the impact on ambulation capacity. Most severe or moderate patients received corticoids and other drugs during hospitalization, which can potentially negatively impact muscle mass and strength. Both hospitalization and the related negative effects associated with medication, sedation, mechanical ventilation, and other interventions, plus the direct and indirect effects of SARS-CoV-2–such as local tissue lesions and secondary damage related to hyper-inflammatory responses–can be associated with functional deficiencies acquired during hospitalization. In fact, post-ICU syndrome associated with SARS-CoV-2 infection could contribute to the explanation of the impact on ambulation capacity [ 39 , 42 , 43 ].

Int. J. Environ. Res. Public Health 2023 , 20 , 7057 8 of 11 Our results reinforce the importance of performing functional assessments and intervention for older adults during hospitalization, especially with regard to the ability to walk. The literature shows that gait speed is an indicator of future adverse health events in the older adult [ 27 ]. In addition, hospitalization itself is considered an aggravating factor for functionality, with a negative impact on mobility and the ability to perform daily activities [ 44 ]. One limitation of this study was the different methods used to assess the ambulation capacity of patients before and during hospitalization. Unfortunately, it was not possible to assess their ambulation capacity before COVID-19 through an evaluation done by physiotherapist, for obvious reasons. However, the participants included in our study presented appropriate cognitive capacity to recall their ambulation capacity before hospitalization However, another limitation of our study was that, despite all hospitalized patients receiving physiotherapy since their first day of hospitalization, unfortunately, we did not collect data regarding the number of sessions of physiotherapy for each patient Due to the high number of patients hospitalized during the pandemic and the lack of health professionals available at that time, unfortunately, it was not possible to screen important risk factors for ambulation impairment, due to factors such as the presence of frailty and sarcopenia in all patients. In fact, this screening was done only in the geriatric unit of our hospital, and it was not possible to use this data to compare with other general units Finally, only a few studies with a small number of participants have evaluated the impairment of ambulation in adults and older adults hospitalized with COVID-19 [ 32 , 33 , 45 ]. Therefore, post-hospital follow-up is necessary to investigate possible people suffering from Post COVID Syndrome [ 46 , 47 ]. Our study, despite the fact that it can only show associations, contributes to filling this gap in the literature and seeks to elucidate the functional impact of COVID-19 on older adults, helping to devise new interventions for COVID-19 prevention and rehabilitation related to this population 5. Conclusions The older patients who died during hospitalization due to COVID-19 had greater gait impairment prior to hospitalization, and more than half of those who were discharged had worsened gait impairment. The main factors associated with impaired ambulation after hospitalization were a hospital stay longer than 20 days; having an impaired gait prior to admission; and being infected by the 2 nd wave of COVID-19. Our results suggest the need for interventions aiming to reduce ambulation impairment in hospitalized older people with severe COVID-19, in order to decrease the risk of longer-term functional impairment in this population Author Contributions: Conceptualization, E.C.G.e.S., J.E.P., C.R.F.C. and C.F.; methodology, E.C.G.e.S and J.E.P.; formal analysis, A.C.B.S., E.C.G.e.S. and J.E.P.; investigation, C.G.d.G. and D.B.d.O.; writing—original draft preparation, E.C.G.e.S., J.E.P., C.R.F.C., C.F., A.C.B.S. and K.D.H.; writing—review and editing, E.C.G.e.S., J.E.P., C.R.F.C., C.F., C.T., C.T.J., C.R.R.d.C. and K.D.H.; funding acquisition, J.E.P All authors have read and agreed to the published version of the manuscript Funding: This study was supported by grants 402698/2020-0 and 312279/2018-3 from the Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Pesquisa (CNPq)), and grant 19618-8/2018 from the S ã o Paulo Research Foundation (Fundaç ã o de Amparo e Pesquisa do Estado de S ã o Paulo (FAPESP)) Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee from the Hospital das Clinicas da Faculdade de Medicina da Universidade de S ã o Paulo, Brazil (number 4.052.246) Informed Consent Statement: Not applicable Data Availability Statement: Where data is unavailable due to privacy or ethical restrictions Conflicts of Interest: The authors declare no conflict of interest.

Int. J. Environ. Res. Public Health 2023 , 20 , 7057 9 of 11 References 1 Zisberg, A.; Shadmi, E.; Sinoff, G.; Gur-Yaish, N.; Srulovici, E.; Admi, H. Low mobility during hospitalization and functional decline in older adults J. Am. Geriatr. Soc 2011 , 59 , 266–273. [ CrossRef ] 2 Mahoney, J.E.; Sager, M.A.; Jalaluddin, M. New walking dependence associated with hospitalization for acute medical illness: Incidence and significance J. Gerontol. A Biol. Sci. Med. Sci 1998 , 53 , M 307–M 312. [ CrossRef ] [ PubMed ] 3 Medina-Mirapeix, F.; Bernabeu-Mora, R.; Garc í a-Guillam ó n, G.; Valera Novella, E.; Gacto-S á nchez, M.; Garc í a-Vidal, J.A. Patterns, Trajectories, and Predictors of Functional Decline after Hospitalization for Acute Exacerbations in Men with Moderate to Severe Chronic Obstructive Pulmonary Disease: A Longitudinal Study PLoS ONE 2016 , 11 , e 0157377. [ CrossRef ] 4 Coppo, A.; Bellani, G.; Winterton, D.; Di Pierro, M.; Soria, A.; Faverio, P.; Cairo, M.; Mori, S.; Messinesi, G.; Contro, E.; et al. Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): A prospective cohort study Lancet Respir. Med 2020 , 8 , 765–774. [ CrossRef ] 5 Morley, J.E.; Vellas, B. Editorial: COVID-19 and Older Adults J. Nutr. Health Aging 2020 , 24 , 364–365. [ CrossRef ] 6 Williamson, E.J.; Walker, A.J.; Bhaskaran, K.; Bacon, S.; Bates, C.; Morton, C.E.; Curtis, H.J.; Mehrkar, A.; Evans, D.; Inglesby, P.; et al. Factors associated with COVID-19-related death using Open SAFELY Nature 2020 , 84 , 430–436. [ CrossRef ] 7 World Health Organization Statement on the Second Meeting of the International Health Regulations (2005) Emergency Committee Regarding the Outbreak of Novel Coronavirus (2019-nCoV) ; World Health Organization: Geneva, Switzerland, 2020. Available online: https://covid 19.who.int/ (accessed on 10 October 2023) 8 Grant, M.C.; Geoghegan, L.; Arbyn, M.; Mohammed, Z.; McGuinness, L.; Clarke, E.L.; Wade, R.G. The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries PLoS ONE 2020 , 15 , e 0234765. [ CrossRef ] 9 Meo, S.A.; Al-Khlaiwi, T.; Usmani, A.M.; Meo, A.S.; Klonoff, D.C.; Hoang, T.D. Biological and epidemiological trends in the prevalence and mortality due to outbreaks of novel coronavirus COVID-19 J. King. Saud. Univ. Sci 2020 , 32 , 2495–2499 [ CrossRef ] 10 Chen, N.; Zhou, M.; Dong, X.; Qu, J.; Gong, F.; Han, Y.; Qiu, Y.; Wang, J.; Liu, Y.; Wei, Y.; et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study Lancet 2020 , 395 , 507–513 [ CrossRef ] 11 Chan, J.F.; Yuan, S.; Kok, K.H.; To, K.K.; Chu, H.; Yang, J.; Xing, F.; Liu, J.; Yip, C.C.; Poon, R.W.; et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster Lancet 2020 , 395 , 514–523. [ CrossRef ] 12 Xu, X.; Chen, P.; Wang, J.; Feng, J.; Zhou, H.; Li, X.; Zhong, W.; Hao, P. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission Sci. China Life Sci 2020 , 63 , 457–460. [ CrossRef ] 13 Tamara, A.; Tahapary, D.L. Obesity as a predictor for a poor prognosis of COVID-19: A systematic review Diabetes Metab. Syndr 2020 , 14 , 655–659. [ CrossRef ] 14 Welch, C.; Greig, C.; Masud, T.; Wilson, D.; Jackson, T.A. COVID-19 and Acute Sarcopenia Aging Dis 2020 , 11 , 1345–1351 [ CrossRef ] 15 Chen, Y.; Klein, S.L.; Garibaldi, B.T.; Li, H.; Wu, C.; Osevala, N.M.; Li, T.; Margolick, J.B.; Pawelec, G.; Leng, S.X. Aging in COVID-19: Vulnerability, immunity and intervention Ageing Res. Rev 2021 , 65 , 101205. [ CrossRef ] 16 Kortebein, P.; Ferrando, A.; Lombeida, J.; Wolfe, R.; Evans, W.J. Effect of 10 days of bed rest on skeletal muscle in healthy older adults JAMA 2007 , 297 , 1772–1774. [ CrossRef ] 17 Marino, D.M.; Marrara, K.T.; Arcuri, J.F.; Candolo, C.; Jamami, M.; Pires Di Lorenzo, V.A. Determination of exacerbation predictors in patients with COPD in physical therapy—A longitudinal study Braz. J. Phys. Ther 2014 , 18 , 127–136. [ CrossRef ] 18 Rawal, G.; Yadav, S.; Kumar, R. Post-intensive Care Syndrome: An Overview J. Transl. Int. Med 2017 , 5 , 90–92. [ CrossRef ] 19 Niu, S.; Tian, S.; Lou, J.; Kang, X.; Zhang, L.; Lian, H.; Zhang, J. Clinical characteristics of older patients infected with COVID-19: A descriptive study Arch. Gerontol. Geriatr 2020 , 89 , 104058. [ CrossRef ] 20 Ferrando, C.; Suarez-Sipmann, F.; Mellado-Artigas, R.; Hern á ndez, M.; Gea, A.; Arruti, E.; Aldecoa, C.; Mart í nez-Pall í , G.; Mart í nez-Gonz á lez, M.A.; Slutsky, A.S.; et al. Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS Intensive Care Med 2020 , 46 , 2200–2211. [ CrossRef ] 21 Gardashkhani, S.; Ajri-Khameslou, M.; Heidarzadeh, M.; Rajaei Sedigh, S. Post-Intensive Care Syndrome in COVID-19 Patients Discharged from the Intensive Care Unit J. Hosp. Palliat. Nurs 2021 , 23 , 530–538. [ CrossRef ] 22 Peghin, M.; Palese, A.; Venturini, M.; De Martino, M.; Gerussi, V.; Graziano, E.; Bontempo, G.; Marrella, F.; Tommasini, A.; Fabris, M.; et al. Post-COVID-19 symptoms 6 months after acute infection among hospitalized and non-hospitalized patients Clin Microbiol. Infect 2021 , 27 , 1507–1513. [ CrossRef ] 23 Simpson, R.; Robinson, L. Rehabilitation following critical illness in people with COVID-19 infection Am. J. Phys. Med. Rehabil 2020 , 99 , 470–474. [ CrossRef ] [ PubMed ] 24 Silva, E.C.G.; Godoy, C.G.; Gambeta, A.C.; Schmitt, A.C.B.; Fu, C.; Tanaka, C.; Carvalho, C.R.F.; Toufen Junior, C.; Carvalho, C.; Pompeu, J.E. Ambulation Capacity, Age, Immunosuppression, And Mechanical Ventilation Are Risk Factors Of In-Hospital Death In Severe COVID-19: A Cohort Study Clinics 2022 , 77 , 100075. [ CrossRef ] [ PubMed ]

Int. J. Environ. Res. Public Health 2023 , 20 , 7057 10 of 11 25 Kamdar, B.B.; Huang, M.; Dinglas, V.D.; Colantuoni, E.; von Wachter, T.M.; Hopkins, R.O.; Needham, D.M.; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Joblessness and lost earnings after acute respiratory distress syndrome in a 1-year national multicenter study Am. J. Respir. Crit. Care Med 2017 , 196 , 1012–1020. [ CrossRef ] 26 Rydingsward, J.E.; Horkan, C.M.; Mogensen, K.M.; Quraishi, S.A.; Amrein, K.; Christopher, K.B. Functional status in ICU survivors and out of hospital outcomes: A cohort study Crit. Care Med 2016 , 44 , 869–879. [ CrossRef ] [ PubMed ] 27 Vrettou, C.S.; Mantziou, V.; Vassiliou, A.G.; Orfanos, S.E.; Kotanidou, A.; Dimopoulou, I. Post-Intensive Care Syndrome in Survivors from Critical Illness including COVID-19 Patients: A Narrative Review Life 2022 , 12 , 107. [ CrossRef ] 28 Berli ´nska, A.; ´Swi ˛ atkowska-Stodulska, R.; Sworczak, K. Old Problem, New Concerns: Hypercortisolemia in the Time of COVID-19 Front. Endocrinol 2021 , 5 , 711612. [ CrossRef ] [ PubMed ] 29 Brasil Minist é rio da Sa ú de Estatuto do Idoso/Minist é rio da Sa ú de , 2 nd ed.; S é rie E. Legislaç ã o de Sa ú de; Editora do Minist é rio da Sa ú de: Bras í lia, Brasil, 2009; 70 p 30 Mehrholz, J.; Wagner, K.; Rutte, K.; Meissner, D.; Pohl, M. Predictive validity and responsiveness of the functional ambulation category in hemiparetic patients after stroke Arch. Phys. Med. Rehabil 2007 , 88 , 1314–1319. [ CrossRef ] [ PubMed ] 31 Lamontagne, F.; Agarwal, A.; Rochwerg, B.; Siemieniuk, R.A.; Agoritsas, T.; Askie, L.; Lytvyn, L.; Agarwal, A.; Leo, Y.-S.; Macdonald, H.; et al. A living WHO guideline on drugs for COVID-19 BMJ 2020 , 370 , m 3379. [ CrossRef ] 32 Pal, C.; Fu, C.; Carvalho, C.R.R.; Auler J ú nior, J.O.C.; Yamauchi, L.Y. Association of the mobility level of critically ill adult patients with the success of extubation: Protocol for a cohort study BMJ Open 2021 , 11 , e 040693. [ CrossRef ] 33 Kemp, H.I.; Corner, E.; Colvin, L.A. Chronic Pain after COVID-19: Implications for Rehabilitation Br. J. Anaesth 2020 , 125 , 436–440. [ CrossRef ] [ PubMed ] 34 Ranzani, O.T.; Bastos, L.S.L.; Gelli, J.G.M.; Marchesi, J.F.; Bai ã o, F.; Hamacher, S.; Bozza, F.A. Characterisation of the first 250,000 hospital admissions for COVID-19 in Brazil: A retrospective analysis of nationwide data Lancet Respir. Med 2021 , 9 , 407–418 [ CrossRef ] [ PubMed ] 35 Tavares, G.S.; Oliveira, C.C.; Mendes, L.P.S.; Velloso, M. Muscle strength and mobility of individuals with COVID-19 compared with non-COVID-19 in intensive care Heart Lung 2023 , 62 , 233–239. [ CrossRef ] [ PubMed ] 36 Meftahi, G.H.; Jangravi, Z.; Sahraei, H.; Bahari, Z. The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: The contribution of “inflame-aging” Inflamm. Res 2020 , 69 , 825–839. [ CrossRef ] 37 Mart í n, J.; Padierna, A.; Anton-Ladislao, A.; Moro, I.; Quintana, J.M. Predictors of mortality during hospitalization and 3 months after discharge in elderly people with and without dementia Aging Ment. Health 2019 , 23 , 1057–1065. [ CrossRef ] 38 Schujmann, D.S.; Lunardi, A.C.; Peso, C.N.; Pompeu, J.E.; Annoni, R.; Miura, M.C.; de Censo, C.M.; Taniguchi, L.N.T.; de Moraes Regenga, M.; de Campos, E.C.; et al. Functional Recovery Groups in Critically Ill COVID-19 Patients and Their Associated Factors: From ICU to Hospital Discharge* Crit. Care Med 2022 , 50 , 1799–1808. [ CrossRef ] 39 Moura, E.C.; Silva EN da Sanchez, M.N.; Cavalcante, F.V.; Oliveira LG de Oliveira, A.; Frio, G.S.; Santos, L.M.P. Timely Availability of Public Data for Health Management: COVID-19 Wave’s Analysis. Available online: https://preprints.scielo.org/index.php/ scielo/preprint/view/2316/version/2454 (accessed on 1 September 2023) 40 Perrotta, F.; Corbi, G.; Mazzeo, G.; Boccia, M.; Aronne, L.; D’agnano, V.; Komici, K.; Mazzarella, G.; Parrella, R.; Bianco, A. COVID-19 and the elderly: Insights into pathogenesis and clinical decision-making Aging Clin. Exp. Res 2020 , 32 , 1599–1608 [ CrossRef ] 41 Stam, H.J.; Stucki, G.; Bickenbach, J.; European Academy of Rehabilitation Medicine. COVID-19 and Post Intensive Care Syndrome: A Call for Action J. Rehabil. Med 2020 , 52 , jrm 00044. [ CrossRef ] 42 Silva Andrade, B.; Siqueira, S.; de Assis Soares, W.R.; de Souza Rangel, F.; Santos, N.O.; Dos Santos Freitas, A.; Ribeiro da Silveira, P.; Tiwari, S.; Alzahrani, K.J.; G ó es-Neto, A.; et al. Long-COVID and Post-COVID Health Complications: An Up-to-Date Review on Clinical Conditions and Their Possible Molecular Mechanisms Viruses 2021 , 13 , 700. [ CrossRef ] 43 Jaffri, A.; Jaffri, U.A. Post-Intensive care syndrome and COVID-19: Crisis after a crisis? Heart Lung 2020 , 49 , 883–884. [ CrossRef ] 44 Freitas, A.R.; Napimoga, M.; Donalisio, M.R. Avaliando a gravidade do COVID-19 Epidemiol. Sa ú de 2020 , 29 , e 2020119 45 Ochiai, G.S.; Godoy, C.G.; Silva, E.C.G.; Oliveira, D.B.; Silva, E.M.; Viana, B.O.C.; Silva, S.M.D.; Souza, R.O.B.; Campos, C.M.; Schmitt, A.C.B.; et al. Functional impact on adults and older people after hospitalization by COVID-19 Physiother. Res. Int 2023 , 28 , e 1983. [ CrossRef ] [ PubMed ] 46 Godoy, C.G.; Silva, E.C.G.; Oliveira, D.B.; Silva, E.M.; Campos, C.M.; Gambeta, A.C.; Carvalho, C.R.F.; Fu, C.; Schmitt, A.C.B.; Tanaka, C.; et al. Protocol for Functional Assessment of Adults and Older Adults After Hospitalization by COVID-19 Clinics 2021 , 76 , e 3030. [ CrossRef ] [ PubMed ] 47 Alonso, A.C.; Silva-Santos, P.R.; Quintana, M.S.L.; Silva, V.C.D.; Brech, G.C.; Barbosa, L.G.; Pompeu, J.E.; Silva, E.C.G.e.; Silva, E.M.D.; Godoy, C.G.D.; et al. Physical and Pulmonary Capacities of Individuals with Severe Coronavirus Disease After Hospital Discharge: A Preliminary Cross-Sectional Study Based On Cluster Analysis Clinics 2021 , 76 , e 3540. [ CrossRef ] [ PubMed ] Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Other Environmental Sciences Concepts:

[back to top]

Discover the significance of concepts within the article: ‘Risk Factors for the Impairment of Ambulation in Older People Hospitalized...’. Further sources in the context of Environmental Sciences might help you critically compare this page with similair documents:

Older people, Daily activities, Clinical data, Public health, Adverse effect, Severe case, Immobility, Data analysis, Functional capacity, Hospital admission, Inclusion criteria, Ethics committee, Muscle Strength, Functional assessment, COVID 19, Functional status, Odds ratio, Confidence interval, Intensive care unit, Post-COVID Syndrome, COVID-19 prevention, Hospitalization, Sarcopenia, Hospital stay, Risk factor, Gait impairment, Functional impairment, Normal Distribution, Statistical difference, COVID-19 Infection, Retrospective cohort study, Tissue damage, Logistic regression, Sociodemographic data, Systemic inflammatory response, Mechanical ventilation, Muscle mass, Neurological disease, Hospital discharge, Clinical characteristic, Severe COVID-19, Multivariate regression model, Invasive mechanical ventilation, Second wave of COVID-19, COVID-19 patient, Post-Intensive Care Syndrome, Sao Paulo, Medical record, Older adult, Impaired gait, Long hospital stay, Loss of mobility, Reduce the risk, COVID-19 wave, Stressful stimuli, In-hospital death, Muscle inactivity, Longer hospital stay, Sociodemographic characteristic, Pandemic wave, Mobility loss.