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SPECIAL SECTION on COVID-19 and PM'R

Hospitalized Patients With COVID-19 and Neurological Complications Experience More Frequent Decline in Functioning and Greater Rehabilitation Needs

Claflin, Edward S. MD; Daunter, Alecia K. MD; Bowman, Angeline MD; Startup, Joshua MD; Reed, Eboni MD; Krishnan, Chandramouli PT, PhD; Kratz, Anna L. PhD

Author Information
American Journal of Physical Medicine & Rehabilitation: August 2021 - Volume 100 - Issue 8 - p 725-729
doi: 10.1097/PHM.0000000000001807
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Abstract

The novel coronavirus, SARS-CoV-2, and the disease, coronavirus disease 2019 (COVID-19),1,2 have led to a global pandemic with millions of cases in the United States alone, resulting in the deaths of more than 450,000 Americans at the time of this writing.3 It has been widely reported that critical illness due to any etiology can result in acute changes in functioning,4 and it is known that related viral diseases, such as severe acute respiratory syndrome and Middle East respiratory syndrome, resulted in significant new impairments in functioning for any patients.5 Indeed, clinical experience around the world has indicated that many of those infected with COVID-19 will experience new functional limitations, including greater dependency with mobility and activities of daily living.6–9

There is a growing body of evidence regarding the systemic effects of SARS-CoV-2 on various organ systems, frequently resulting in new neurological and musculoskeletal impairments.10–14 Other studies have suggested that multiorgan disease is present in even mild and moderate diseases.15 It has also been shown that other human coronavirus infections penetrate into the human cerebrospinal fluid.16 In line with these data, a multicenter, retrospective study reported neurological manifestations in 36.4% of patients admitted with COVID-19,17 and a recent meta-analysis reported prevalence rates for neurological symptoms in patient with COVID-19. Information about the outcomes of these patients has important clinical and public health implications, as neurological impairments and functional limitations will impact hospital discharge planning, distribution of postacute resources, and accurate assessment of prognosis. This is particularly true given the magnitude of the public health crisis underway.

Therefore, the primary aim of this study was to compare patients with and without serious neurological sequelae in terms of functional outcomes and duration of inpatient care during their admission to our hospital due to acute COVID-19 infection. We hypothesized that hospitalized patients with COVID-19 infection and neurological complications would demonstrate greater decline in physical function, longer length of stay, and greater postacute needs than those without neurological complications.

METHODS

DataDirect (The University of Michigan Health System) software was used to identify people admitted to a single tertiary care hospital in the Detroit metro area, with a laboratory-confirmed diagnosis of COVID-19. Individual medical records were reviewed by practicing physical medicine and rehabilitation physicians. Each case was confirmed to have a laboratory-verified diagnosis of COVID-19 occurring during the time of the hospitalization. Patients who were not positive for COVID-19 during an admission were excluded. Children younger than 18 yrs were also excluded from analysis.

Individual hospital medical records were reviewed, including admission and discharge notes; physical, occupational, and speech language pathology records; progress notes; radiology results; case management notes; and relevant physical medicine and rehabilitation or neurology consultations. No informed consent was obtained as the study was reviewed and determined to be exempt by the University of Michigan Institutional Review Board.

Data were collected regarding preexisting neurological diagnoses, neurological imaging studies performed, neurological symptoms observed, discharge location, length of stay, and any new neurological diagnoses made. Length of stay was tracked for our institution only, not including days spent at other facilities before transfer. Each case was primarily reviewed by one physician, and 80 chart audits were conducted by the first author to ensure the integrity of the data. Although incomplete data were noted, the chart audits revealed no errors.

Patients with documented delirium, encephalopathy, and altered mental status were included as well as any patients with documented central nervous system abnormality. Patients who died while on sedation/ventilation were not considered to have had neurological complications unless their sedation was weaned and neurological abnormalities were documented. Headache, dizziness, and impairments of smell or taste were not reported consistently in the clinical documentation and are not reported here as serious neurological sequelae. Rates of these complications have been reported elsewhere.17,18

For those who survived to hospital discharge, charts were also reviewed to identify and understand functional changes that were impacting the patient at the time of discharge. Patients were considered to have experienced an acute functional decline if they required physical, occupational, and/or speech and language pathology referral at discharge; additional caregiver assistance for mobility or activities of daily living; new durable medical equipment needs (excluding home oxygen alone); or diet modifications for dysphagia. When none of these characteristics were present, it was assumed that no functional decline was apparent.

Descriptive statistics (frequencies, mean, range, standard deviation) were calculated for all variables. The normality of the distribution for each of the variable was evaluated using Q-Q plots and Kolmogorov-Smirnov tests. Group differences in frequencies were tested with χ2 statistics, and group differences in means were tested with two-sample t tests for normally distributed data (i.e., age) and with Kruskal-Wallis H tests for nonnormally distributed data (i.e., length of stay). After a significant omnibus χ2 test for discharge location by neurological status, we used nonparametric one-sample binomial tests to evaluate whether the likelihood of the occurrence of neuro-COVID versus COVID-19 was equal (pairwise test proportion = 0.5) within each discharge subcategory. An α value of 0.05 was set as the critical P value. All analyses were conducted using IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp, Armonk, NY).

RESULTS

Subject Characteristics

Three hundred twenty potential cases were reviewed, with admission dates between March 4, 2020, and May 1, 2020. Five were excluded from analysis because of age of younger than 18 yrs. Sixteen cases were excluded because of asynchronous COVID-19 diagnosis and hospitalization dates (i.e., the person was never diagnosed with COVID-19 during the inpatient admission). Three were excluded from analysis because of being currently admitted at the time of data analyses. The final number of cases included in analysis was 296 (Fig. 1).

F1
FIGURE 1:
Flow chart of medical charts reviewed. A list of patients who had an acute hospital admission and a positive diagnosis of COVID-19 within the date range specified was obtained, and these charts were evaluated by the criteria noted.

Of these patients admitted with acute COVID-19 infection, 81 (27.4%) experienced documented neurological manifestations during their acute hospitalization (henceforth referred to as neuro-COVID patients). Characteristics of the patients with and without neurological manifestations are summarized in Table 1. Statistically significant differences were observed in age (P < 0.001), length of stay (P < 0.0001), and proportion of patients transferred from outside hospital (P = 0.002), with the neuro-COVID group demonstrating older average age and longer lengths of stay and greater proportion of patients admitted from another hospital.

TABLE 1 - Demographic differences between all patients admitted for acute management of COVID-19 and patients with COVID-19 complicated new neurological diagnosis/diagnoses
COVID-19 Patients a Neuro-COVID Patients Difference
n (%) n (%)
Total patients 215 (72.6) 81 (27.4)
Sex
 Female 94 (43.7) 31 (38.3) χ2 (1, N = 296) = .72, P = 0.40
 Male 121 (56.3) 50 (61.7)
Race χ2 (4, N = 296) = 6.99, P = 0.14
 White 90 (41.9) 38 (46.9)
 African American 92 (42.8) 37 (45.7)
 Asian 9 (4.2) 1 (1.2)
 Other 13 (6.0) 0 (0)
 Unknown 11 (5.1) 5 (6.2)
Transfer from outside hospital 32 (14.9) 25 (30.9) χ2 (1, N = 296) = 9.66, P = 0.002
Mean (SD) Mean (SD)
Age (all; min–max = 20–95 yrs) 60.21 (14.56) 66.11 (15.99) t (294) = −3.03, P = 0.003
Age (survivors; min–max = 20–95 yrs) 59.02 (14.14) 64.70 (16.64) t (245) = −2.63, P = 0.02
Age (deceased; min–max = 30–90 yrs) 67.29 (15.22) 71.06 (12.68) t (47) = −0.89, P = 0.36
Length of stay (all) 10.19 (10.11)
Min–max = 0–61
22.78 (16.07)
Min–max = 2–75
H (1) = 52.47, P < 0.0001
Length of stay (survivors) n = 247 9.78 (10.26)
Min–max = 0–61
24.35 (16.33)
Min–max = 2–75
H (1) = 49.67, P < 0.0001
Length of stay (deceased) n = 49 12.58 (8.94)
Min–max = 1–35
17.28 (14.19)
Min–max = 5–65
H (1) = 1.71, P = 0.19
aIndicates patients without neurological changes.

Survivor Functional Decline

Of the 247 patients with COVID-19 who survived to acute hospital discharge or transfer, neuro-COVID patients experienced a significantly higher rate of functional decline (P < 0.0001) as summarized in Table 2. However, within the subsample of patients with new functional decline, neuro-COVID patients did not require significantly more frequent need for ongoing therapy services at the time of acute hospital discharge (P = 0.16) or more frequent need for new durable medical equipment (P = 0.24). Neuro-COVID patients did show significantly greater frequency of new dysphasia (P < 0.0001) and longer length of stay (P = 0.001).

TABLE 2 - Differences in rate of new functional decline in patients without neurological complications of COVID-19 versus patients with neurological complications of COVID-19
COVID-19 Patients a Neuro-COVID Patients
n (%) n (%) Difference
Total patients 215 (72.6) 81 (27.4)
New functional decline Yes 60 (32.6) 53 (84.1) χ2 (1, n = 247) = 50.19, P < 0.0001
No 124 (67.4) 10 (15.9)
Subsample of patients who showed new functional decline (n = 113)
Referred for additional therapy services at discharge Yes 43 (82.7) 46 (92.0) χ2 (1, n = 102) = 1.99, P = 0.16
No 9 (17.3) 4 (8.0)
Required new DME Yes 36 (73.5) 40 (83.3) χ2 (1, n = 97) = 1.39, P = 0.24
No 13 (26.5) 8 (16.7)
New dysphagia Yes 7 (11.7) 25 (47.2) χ2 (1, n = 113) = 17.75, P < 0.0001
No 53 (88.3) 28 (52.8)
Mean (SD) Mean (SD)
Total length of stay 17.77 (13.42) 27.00 (15.93) H (1) = 11.89, P = 0.001
The lower portion of the table compares these two groups with regard to portion of patients referred for outpatient therapy referrals, requiring new DME, diagnosed with new dysphagia, and total length of stay in the subset of patients who did demonstrate new functional decline.
aIndicates patients without neurological changes.

Discharge Location

Results shown in Table 3 display the significant differences in hospital discharge location comparing patients admitted with COVID-19 without neurological changes and patients with acute COVID-19 who developed neurological sequelae (χ2 (5, N = 296) = 71.645, P < 0.0001). Neuro-COVID patients were significantly less likely to be discharged home (P < 0.0001) and significantly more likely to be discharged to subacute rehabilitation/skilled nursing facility (P < 0.0001). A total of 75.8% of COVID-19 patients without neurological sequelae were discharged to home, whereas 30.9% of neuro-COVID patients were discharged to home. A disproportionate number of patients with neurological sequelae were discharged to subacute rehabilitation/skilled nursing facility (25.9%) compared with those without neurological sequelae (8.8%). Neurological status during hospitalization did not relate to differences in discharge to acute inpatient rehabilitation, long-term acute care hospital, or hospice (P > 0.05). Neuro-COVID patients were more likely to die before discharge (22.2%) compared with non–neuro-COVID patients (14.4%, P < 0.0001).

TABLE 3 - Differences in acute hospital discharge location for all patients admitted with COVID-19 versus patients with COVID-19 who also experiences serious neurological sequelae
COVID-19 Patients, a n (%) Neuro-COVID Patients, n (%) Difference
Total patients 215 (72.6) 81 (27.4)
Home 163 (75.8) 25 (30.9) P < 0.0001
SAR/SNF 19 (8.8) 21 (25.9) P < 0.0001
Acute inpatient rehabilitation 2 (0.9) 7 (8.6) P = 0.180
LTACH 0 (0) 5 (6.2) P = 0.062
Hospice 0 (0) 5 (6.2) P = 0.062
Deceased 31 (14.4) 18 (22.2) P < 0.0001
Note that the P values indicate whether the likelihood of the occurrence of neuro-COVID versus COVID-19 was significantly different within each discharge category.
aIndicates patients without neurological changes.
SAR/SNF, subacute rehabilitation/skilled nursing facility; LTACH, long-term acute care hospital.

DISCUSSION

As the global pandemic continues and people continue to endure the consequences of COVID-19, it is important that countries, health systems, and providers be aware of the impact of the disease on the functioning of their patients, and it is necessary that we accurately identify and optimally manage those who feel the impact most. Other studies have indicated that patients with more severe respiratory illnesses do experience greater functional impact5 and that appropriate rehabilitation can ameliorate these deficits.4,19 It has also been reported that patients with COVID-19 experience neurological symptoms and sequelae at significant rates18 and that patients with more severe illness demonstrate higher rates of COVID-19 symptoms as well as higher rates of central nervous system symptoms.17 Our work on a large cohort of patients admitted during the early months of the pandemic further extends these previous findings by showing, for the first time, that individuals with neurological complications due to COVID-19 have greater functional decline and postacute needs. The findings of this study will better prepare patients, providers, and health systems for the postacute needs of those infected with COVID-19 who have neurological complications.

This article demonstrates that patients hospitalized with COVID-19 who develop serious neurological impairments, including those with delirium/encephalopathy/altered mental status, have significantly longer length of stay, higher rate of functional decline, worse mortality, and greater need for ongoing rehabilitation. These findings agree with clinical experience20 and should enable providers to more rapidly recognize the additional rehabilitation needs of these patients and act accordingly.

Certain limitations apply, including the uncertain ability to generalize these findings from the early pandemic period to the current time and the ability to generalize to the broader global population. Although an in-depth chart review was completed for all patients included in this analysis, it is possible that all patients with serious neurological sequelae were not captured. Given the observational nature of this study, some patients who experienced delirium/encephalopathy may not have been identified if the documentation was ambiguous or incomplete. In addition, prevalence rates of various neurological sequelae from COVID-19 will certainly vary within and between populations.

Research has begun21 and should continue to define the rehabilitation needs and optimal treatment strategies for COVID-19 survivors. In line with this study, future investigation might focus on the best time to initiate therapies, intensity of rehabilitation interventions, and location and type of services provided. This information will enable multidisciplinary teams to mobilize the necessary resources to provide the best possible care to those affected by COVID-19.

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Keywords:

SARS-CoV-2; Neurologic; Morbidity; Function; Hospital Stay

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