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SPECIAL SECTION on COVID-19 and PM&R

Predictors of Functional Dependence After COVID-19

A Retrospective Examination Among Veterans

Leigh, Alexandra E. MD; McCall, Jonathan MD, MPH; Burke, Rebecca V. MD; Rome, Robin APRN; Raines, Amanda M. PhD

Author Information
American Journal of Physical Medicine & Rehabilitation: January 2021 - Volume 100 - Issue 1 - p 34-38
doi: 10.1097/PHM.0000000000001614

Abstract

What Is Known

  • Although much has been reported on the correlates and consequences of COVID-19 mortality, less is known about the factors associated with functional status at discharge among hospitalized patients.

What Is New

  • Retrospective chart reviews were conducted on 119 veterans hospitalized for COVID-19 infection. Increased patient age, respiratory failure, cardiac conditions, and most markedly thromboembolic complications during COVID-19 hospitalization increased the odds of functional dependence in activities of daily living at discharge. In essence, patient age and measures of severe COVID-19 infection are more predictive of functional dependence at discharge than comorbid conditions before infection.

The risk of severe COVID-19 infection varies with demographics and preexisting medical conditions, including increased age, diabetes, cardiovascular disease, and underlying lung disease.1,2 Severe COVID-19 infection is associated, in some, with a prolonged recovery phase measuring a month or more.3 Analyses of patients discharged with COVID-19 have not reported on the functional abilities or limitations of patients following hospitalization at discharge.3,4 At present, the clinical data on the post–acute care needs of COVID-19 patients is limited. Moreover, understanding the association between patient characteristics and COVID-19 infection on functional status after hospitalization is of critical importance for setting patient and family expectations, health system planning and staffing, and predicting rehabilitation utilization.

For non-COVID-19 patients requiring hospitalization, predictors of decreased functional status from admission to discharge have been examined. In one study examining adult intensive care unit (ICU) patients, length of ICU admission, poor health before hospitalization, and a long period of mechanical ventilation were the strongest predictors of decreased functionality.5 In elderly patients, admission from a nursing home, increased length of hospital stay, baseline dependence in activities of daily living (ADLs), underlying cardiovascular disease, congestive heart failure, chronic obstructive pulmonary disease, dementia, and hypoalbuminemia correlated with decreased functional status. Admitting disease severity has also been found to correlate with poor functional status at discharge.6 Thus, many factors from the three domains of baseline demographics, preexisting health conditions, and disease severity during hospitalization increase the risk of poor function at discharge for patients without COVID-19 infection.

Severe COVID-19 infection has also been compared with acute respiratory distress syndrome (ARDS), and there is concern that post–intensive care syndrome, defined as the cognitive and physical debility that persists beyond discharge, will likewise be a consequence in many surviving COVID-19.7 Patients with ARDS who survive to hospital discharge have lower-than-normal population scores in functional disability that persist 1 and 2 yrs after discharge.8,9 For long-term survivors, 5 yrs after ARDS, patients still suffer with decreased walking distance and physical activities compared with individuals without ADRS.8 Older age, prehospitalization morbidity, and ICU disease severity have been associated with worse physical outcomes after discharge for ARDS patients.10 Unanswered is whether older age, preexisting conditions, and COVID-19 severity similarly predict worse COVID-19 functional outcomes.

The Southeast Louisiana Veterans Healthcare System (SLVHCS) is a medical center located in New Orleans providing health care to veterans throughout 23 parishes in Southeast Louisiana.11 SLVHCS identified the first COVID-19-positive patient in the state of Louisiana and shortly thereafter cared for a surge of COVID-19 patients.12 This cohort of patients provided a lens into the unforeseen complexities of discharging patients hospitalized with COVID-19. An analysis of New Orleans patients found that Black patients were hospitalized at a higher rate than White patients in the city, but after adjustment for baseline differences in sociodemographic and preexisting conditions, Black race was no longer associated with a higher mortality rate.13 Given this backdrop, this study sought to describe the functional status dependency in a cohort of patients admitted to the authors’ facility, SLVHCS, during the surge of COVID-19 cases in the city of New Orleans, LA, by unearthing the characteristics that were associated with dependence in ADLs at discharge.

MATERIALS AND METHODS

Selection and Description of Participants

A cohort of COVID-19-positive patients was constructed using health administrative databases capturing all polymerase chain reaction–positive COVID-19 tests among veterans presenting to the SLVHCS hospital. Records for all patients with COVID-19-positive tests between March 1, 2020, and April 20, 2020, were extracted from the computerized patient record system and entered into a deidentified database. All COVID-19-positive veterans were included in this study cohort; eight patients who were not yet discharged by May 18, 2020, were removed from the analyses. Given that this study examined the functional status of patients at discharge, deceased patients were also excluded from the analyses. Data were collected retrospectively; therefore, informed consent was not obtained. Nevertheless, the VA Institutional Review Board approved the use of these data for research purposes. This study conforms to all strengthening the reporting of observational studies in epidemiology guidelines and reports the required information accordingly (see Supplemental Checklist, Supplemental Digital Content 1, http://links.lww.com/PHM/B151).

Outcome Variable

Veteran functional status at discharge, as measured by independence or dependence (including partial dependence or fully dependent) in ADLs, was the main outcome variable for this study.

Functional status at discharge was ascertained by chart review from occupational therapy inpatient notes, physical therapy inpatient notes, and physician discharge summaries. At the authors’ hospital, ADLs must be reported in the standardized physician discharge summary; they are also reported in every occupational therapy and in rare, when witnessed, physical therapy notes. Occupational therapy notes at this hospital are narrative but are written after a bedside evaluation that includes dressing, the ability to bath in a sink or shave, self-feeding, and toileting; standardized ADL measures and tools are not used. If a patient required assistance with any ADL in the final assessment before discharge, they were marked as dependent in the analysis in this study. Of note, a patient requiring supervision alone was marked as independent in this study’s analysis. In addition, ADL functionality before hospital stay was gathered by patient self-report (or surrogate self-report when patient unable to relate) recorded in the above notes.

Of note, ADL function before hospitalization was not included in the results as early analysis showed that as a variable, it was highly correlated with functional status at discharge; moreover, the purpose of this analysis was to find the factors that predicted decreased functional status at discharge rather than change in functional status during hospitalization.

Potential Predictor Variables

Previous studies have demonstrated poorer outcomes in COVID-19 patients with the high-risk conditions of age older than 65 yrs, nursing home or long-term care facility residents, and people of all ages with underlying medical conditions, particularly if not well controlled. At the time of the analysis in early May 2020, the Centers for Disease Control and Prevention listed the following high-risk underlying medical conditions: chronic lung disease or moderate to severe asthma, serious heart conditions, immunocompromised conditions, severe obesity (body mass index ≥40 kg/m3), diabetes mellitus, chronic kidney disease undergoing dialysis, and liver disease.14 Using the Centers for Disease Control and Prevention list as a guide, and including some measures of functional ability before admission, predictor variables included in this study included patient age, sex, marital status, race, site of living before admission, if living alone before admission, and independence in ADLs before admission (Table 1). Medical history included body mass index, hypertension, diabetes, glomerular filtration rate less than 60 mL/min/1.73 m2, underlying vascular disease (heart, stroke, peripheral), underlying lung disease, and history of or active cancer (excluding skin cancers). Factors that examined the severity of the illness course included requiring oxygen by nasal cannula, requiring high-flow nasal cannula, requiring bilevel positive airway pressure, requiring mechanical ventilation, requiring ICU admission, requiring new dialysis, new thromboembolic diagnosis (deep vein, pulmonary embolism or other clots including dialysis line clots), new cardiac findings (increased troponin, myocardial infarction, or arrhythmia), elevated liver function tests, and new delirium or central nervous system findings (including stroke, seizures, and altered mental status not classified as delirium).

TABLE 1 - Demographics, preexisting medical conditions, and prehospital functionality among patients who survived until discharge
Total (N = 119) Status on Discharge
Independent in ADLs (n = 85) Partially or Fully Dependent in ADLs (n = 34)
Baseline characteristics
 Age, mean (SD), years 64.95 (12.43) 61.67 (11.82) 73.15 (10.12)
 Male 111 (93.3) 77 (90.6) 34 (100)
 Black 102 (85.7) 72 (84.7) 30 (88.2)
 Married/partnered 67 (56.3) 46 (54.1) 21 (61.8)
 Living alone before admission 33 (27.7) 30 (35.3) 3 (8.8)
 Nursing home/group living before admission 9 (7.6) 1 (1.2) 8 (23.5)
Preexisting medical conditions
 Dependent in ADLs before admission 18 (15.1) 0 (0) 18 (52.9)
 Hypertension 90 (75.6) 60 (70.6) 30 (88.2)
 Diabetes mellitus 46 (38.7) 30 (35.3) 16 (47.1)
 BMI >40 kg/m3 14 (11.8) 11 (12.9) 3 (8.8)
 Underlying cardiovascular and/or cerebrovascular disease 27 (22.7) 15 (17.6) 12 (35.3)
 GFR <60 mL/min/1.73 m2 25 (21.0) 17 (20) 8 (23.5)
 Underlying lung disease 11 (9.2) 6 (7.1) 5 (14.7)
 Malignancy or history of malignancy 19 (16.0) 13 (15.3) 6 (17.6)
 No. of comorbidities, mean (SD) 1.95 (1.31) 1.79 (1.30) 2.36 (1.25)
COVID-19, conditions diagnosed during hospital stay
 Required nasal cannula O2 82 (68.9) 58 (68.2) 24 (70.6)
 Respiratory failure 26 (21.8) 12 (14.1) 14 (41.2)
 Thromboembolic disease 12 (10.1) 2 (2.4) 10 (29.4)
 Delirium 16 (13.4) 5 (5.9) 11 (32.4)
 New cardiac disease 23 (19.3) 8 (9.4) 15 (44.1)
 Elevated liver function test 45 (37.8) 32 (37.6) 13 (38.2)
 Length of stay, mean (SD), days 8.87 (9.36) 5.79 (4.71) 16.56 (13.09)
 ICU stay 30 (25.2) 15 (17.6) 15 (44)
Data are presented as n (%), unless otherwise indicated.
BMI indicates body mass index; GFR, glomerular filtration rate.

Findings were divided into those patients who were and were not dependent in ADLS at discharge. In addition, underlying comorbidities were tallied to see whether cumulative comorbidities were predictive of functional status at discharge. A body mass index greater 40 kg/m2, defined by the Centers for Disease Control and Prevention as a risk factor as of May 2020, was included as a comorbidity10 (Table 1).

Because of some groups having fewer than five cases, like variables were condensed to reflect overarching organ system failure. Respiratory failure was condensed from the following three groups: the need for high-flow nasal cannula, bilevel positive airway pressure, and/or mechanical ventilation. Furthermore, because of some groups having fewer than five cases, some variables were removed; these included developments of renal failure requiring dialysis and new central nervous system findings.

Data Analytic Plan

Before conducting analyses, data screening was performed. This included running descriptive statistics to check for data entry errors, missing data, and outliers. Next, zero-order correlations among all predictor variables and the outcome of interest were examined to assess for multicollinearity (as evidenced by high intercorrelations among the variables) and to identify relevant predictors to be included in the model. Finally, a hierarchical logistic regression analysis was performed to examine the impact of various demographic and medical variables on functional status at discharge. Step 1 of the model included relevant demographics, step 2 included the number of preexisting medical conditions, and step 3 included medical complications that developed during the COVID-19 hospital stay. Only those variables significant at the zero-order level were included in the hierarchical logistic regression.

RESULTS

Preliminary Analyses

Regarding zero-order correlations, there was a significant association between functional status at discharge and veteran age (r = 0.42, P < 0.001) but not veteran sex, race, or marital status (P values > 0.07). There were significant associations between living status (r = −0.27, P = 0.003) and nursing/group home status (r = 0.38, P < 0.001) and the outcome of interest, functional dependence at discharge. Furthermore, there was a significant association between the functional status at discharge and the combined number of preexisting medical conditions (r = 0.20, P = 0.032) as well as the following conditions diagnosed during hospital stay: respiratory failure (r = 0.30, P = 0.001), delirium (r = 0.35, P < 0.001), cardiac conditions (r = 0.40, P < 0.001), and thromboembolic complications (r = 0.41, P < 0.001). However, there was not a significant association between discharge status and the requirement of a nasal cannula or elevated liver function test (P values > 0.80); thus, these variables were not included as predictors in the hierarchical logistic regression model. Furthermore, the intercorrelations between respiratory failure, ICU status, and length of stay were high (r values > 0.80). Therefore, consistent with the recommendation of Berry and Feldman,15 ICU status and length of stay were not included in the logistic regression because of possible issues with multicollinearity among the predictors.

Primary Analyses

A hierarchical logistic regression was performed to examine the impact of various medical conditions diagnosed during hospital stay on functional status at discharge after controlling for relevant demographics and the number of preexisting medical conditions. Step 1 of the model, which included patient age, explained between 19% (Cox and Snell R2) and 27% (Nagelkerke R2) of the variance in discharge status, with 78.2% of cases correctly identified. Step 2 of model, which included the number of preexisting medical conditions, explained between 20% (Cox and Snell R2) and 28% (Nagelkerke R2) of the variance in discharge status, with 77% of cases correctly identified. The third and final step of the model, which included respiratory failure (a grouping that included the need for high-flow nasal cannula, bilevel positive airway pressure, and mechanical ventilation), delirium, cardiac conditions, and thromboembolic complications, explained between 40% (Cox and Snell R2) and 57% (Nagelkerke R2) of the variance in functional status at discharge, with 85% of cases correctly identified. The full model containing all predictors was statistically significant (χ26 [N = 119] = 59.85, P < 0.001). As shown in Table 2, only four of the independent variables made a statistically significant contribution to the final model, with new thromboembolic complications during COVID-19 hospitalization evincing the strongest association (odds ratio, 25.58).

TABLE 2 - Summary of hierarchical logistic regression analysis
Variable B SE Wald df P Odds Ratio
Step 1: relevant demographics
 Age 0.10 0.03 16.71 1 <0.001 1.11
Step 2: preexisting conditions
 Combined number of preexisting conditions 0.14 0.18 0.62 1 0.431 1.15
Step 3: COVID-19, conditions diagnosed during hospital stay
 Respiratory failure 1.63 0.80 4.14 1 0.042 5.12
 Thromboembolic complications 3.24 1.25 6.75 1 0.009 25.58
 Delirium 0.86 0.76 1.27 1 0.259 2.36
 Cardiac conditions 1.28 0.64 3.99 1 0.046 3.58
Bold denotes significance.

DISCUSSION

In this retrospective analysis, it was found that functional dependence in ADLs after COVID-19 infection requiring hospitalization was significantly associated with increased patient age, respiratory failure, development of COVID-19-related cardiac conditions, and most predominately new thromboembolic complications diagnosed during COVID-19 hospitalization. In essence, factors associated with COVID-19 infection severity were more predictive of functional status dependence at discharge than underlying health conditions before infection or patient demographics, somewhat in contrast to patients without COVID-19 requiring hospitalization and ICU stays. For discharge planning and rehabilitation teams, this information provides evidence that it is the gravity of the COVID-19 infection that correlates with a dependent functional status at discharge more than demographics and preexisting medical conditions, aside from older age.

The results of this study showed that the development of thromboembolic complications had a much higher odds ratio than any other variable in predicting functional dependence at discharge. It may be that the overwhelming activation of the thrombosis pathway that develops in some patients, and not others, correlates highly with the seriousness of infection, along the same spectrum as the processes causing death in COVID-19. Alternatively, the unique hyper-coagulable pathway that is activated in some patients may lead to processes that cause increased muscular weakness, length of stay, and thus dependence in functional status independent of COVID-19 processes causing death. Some authors, after autopsy studies, have hypothesized that younger patients with less underlying comorbidities who develop severe infection have lung involvement predominate (characterized by diffuse alveolar damage), whereas those patients who are older with serious comorbidities may tend more to the thrombosis and multiorgan failure pathway of COVID-19 infection.16 The trifecta of respiratory failure, cardiovascular conditions, and thromboembolic complications that were found significant in predicting functional dependence may follow the multiorgan failure pathway that may have thrombophilia as its predominate defining characteristic.

Multiple studies have documented the high incidence of hypercoagulability detected in critically ill COVID-19 patients. Many mechanisms have been proposed for the pathogenesis of coagulopathy seen in COVID-19 infection, including endothelial inflammation, hypoxemia causing vasoconstriction and release of factors impairing fibrinolysis leading to fibrin deposition, and a predominance of lupus anticoagulant (noted in 50/57 tested patients by Helms et al.17). Autopsy studies have yielded information on this phenomenon. Both the venous (deep venous thrombosis, pulmonary embolism, occlusion of indwelling catheters) and arterial (strokes, myocardial ischemia) systems have been implicated. In one Swiss paper, “massive capillary congestion, often accompanied by microthrombi despite anticoagulation” was seen.18 In another study of consecutive autopsy patients, large thromboses were seen in either the deep venous or pulmonary system in 58% of the deaths.16 It seems that this hypercoagulable phenotype is specific to COVID-19 and different from traditional disseminated intravascular coagulation.17 Likewise, abnormal coagulation laboratory parameters (D-dimer and fibrin degradation products) portended a significantly higher mortality rate for patients with COVID-19 pneumonia compared with those patients who survive.19,20

The implications of increased functional dependence at discharge after COVID-19 infection bear much in common with the discharge of those with ARDS and post–intensive care syndrome. Expert consensus has established that for all with post–intensive care syndrome, direct access to physical therapy after discharge with goals of increased ADL function, mobility, strength, and quality of life is imperative.21 Certainly, patients with functional debility due to COVID-19 need to be examined to assess outcomes when rigorous postdischarge support is offered. Only time and further studies will show the true implications of healthcare need for these patients weeks, months, and years from now.

Potential limitations of this study include a small sample size and a predominately male, veteran, and Black population. Veteran populations treated by the Veteran’s Health Administration, such as SLVHCS, are older, more medically ill, and more socioeconomically disadvantaged.22 This limits the generalizability of the study but also highlights an important demographic contribution as many communities with COVID-19 surges have shared some of these patient characteristics. Another limitation is that in the time since this analysis was completed, the Centers for Disease Control and Prevention has altered the list of those conditions associated with an increased risk of severe COVID-19 infection and those conditions were not captured in this study. Further studies should correct for these updates. In addition, physician and therapist reports used to capture functional status for some patients at discharge were narrative, rather than using standardized ADL measurement tools. Additional studies should evaluate, based on these findings, the level of care needed after discharge for COVID-19 patients, including inpatient rehabilitation, home therapy services, and nursing home placement, and use standardized measures for ADL function and consider the addition of mobility measures. Future studies should seek to use a much larger, demographically diverse sample, followed over a longer period to determine whether these relationships still stand. Given the small window of time in which data were culled, the authors were unable to assess change in functional status as a result of COVID-19 hospitalization. They recommend establishing the functional baseline and then the post–hospital stay change in functionality and mobility with standardized measures.

CONCLUSIONS

Thromboembolic phenomena associated with COVID-19 infection severity were most predictive of functional dependence in ADLs after hospitalization with COVID-19. Underlying demographics, aside from age and underlying health conditions, were not associated with functional status dependency in the patients in this study, despite the known importance of such variables in predicting death from COVID-19.1 Further research is needed to understand whether the associations found in this analysis are truly predictive.

ACKNOWLEDGMENTS

The authors thank the veterans and their families of the Southeastern Veterans Health Care System for allowing us to participate in their care.

REFERENCES

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11. US Department of Veterans Affairs, Veterans Health Administration: About the Southeast Louisiana Veterans Health Care System. Available at: www.neworleans.va.gov/about/index.asp. Accessed May 5, 2020
12. Louisiana Department of Health: COVID-19 news. Available at: http://ldh.la.gov/Coronavirus/. Accessed May 20, 2020
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15. Berry WD, Feldman S: Multiple Regression in Practice (Quantitative Applications in the Social Sciences). Thousand Oaks, CA, SAGE Publications, 1985
16. Wichmann D, Sperhake JP, Lütgehetmann M, et al.: Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med 2020;173:268–77
17. Helms J, Tacquard C, Severac F, et al.: High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 2020;46:1089–98
18. Menter T, Haslbauer JD, Nienhold R, et al.: Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology 2020;77:198–209
19. Tang N, Li D, Wang X, et al.: Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020;18:844–7
20. Zhou F, Yu T, Du R, et al.: Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054–62
21. Major ME, Kwakman R, Kho ME, et al.: Surviving critical illness: What is next? An expert consensus statement on physical rehabilitation after hospital discharge. Crit Care 2016;20:354
22. Anhang Price R, Sloss EM, Cefalu M, et al.: Comparing quality of care in Veterans Affairs and non–Veterans Affairs settings. J Gen Intern Med 2018;33:1631–8
Keywords:

COVID-19; Activities of Daily Living; Functional Status; Thrombosis; Veterans

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