Post-Intensive Care Syndrome Associated With Coronavirus Disease: A Single Institutional Study In Tokyo

doi:10.21203/rs.3.rs-387067/v1

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Post-Intensive Care Syndrome Associated With Coronavirus Disease: A Single Institutional Study In Tokyo

https://doi.org/10.21203/rs.3.rs-387067/v1

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Background: The occurrence of post-intensive care syndrome (PICS) in critically ill patients with coronavirus disease (COVID-19) remains unclear. This study aimed to investigate the physical, mental, and cognitive components of PICS in intensive care unit (ICU)-treated COVID-19 survivors.

Methods: This prospective cohort study enrolled patients with COVID-19 who were treated in the ICU of a single institution between March 19, 2020 and April 30, 2020. A survey was sent by postal mail at 4 and 6 months after ICU discharge. The questionnaire comprised the post-COVID-19 functional status (PCFS) scale and the modified medical research council dyspnea scale (mMRC) for assessing physical PICS; the impact of event scale-revised (IES-R) and the hospital anxiety and depression scale (HADS) for assessing mental PICS; and self-assessment questions for concentration, memory, and forgetfulness for assessing cognitive PICS. Physical PICS was defined by a PCFS or mMRC score ≥1. Mental PICS was defined by an IES-R score ≥25 or if the HADS score for anxiety or depression components was ≥8. Cognitive PICS was defined according to patient complaints of deterioration in concentration, memory, or forgetfulness. The primary outcome was PICS occurrence at 4 months. Moreover, we assessed the co-occurrence of the three PICS components.

Results: Twenty patients consented to participate in the study and responded to the survey. The median age was 57.5 years, and 80% of the patients were male; moreover, 50%, 55%, and 80% lived alone, were married, and were employed/self-employed before hospitalization, respectively. During ICU stay, 80%, 75%, and 25% received invasive mechanical ventilation, systemic steroids, and continuous benzodiazepine, respectively. Delirium occurred in 40% of patients. The median days of ICU and hospital stay were 6 and 21, respectively. Physical, mental, and cognitive PICS occurred in 14 (78%), 9 (45%), and 11 (55%) patients, respectively. There were 16 (80%) and 8 (40%) patients with at least one and all PICS components, respectively.

Conclusions: Our findings revealed a high rate of PICS in COVID-19 survivors. Long-term and comprehensive evaluation of all three PICS components is crucial for providing appropriate care to these patients.

Critical Care & Emergency Medicine

COVID-19

post-intensive care syndrome

ICU

critical care

physical

mental

cognitive

questionnaire

survey

A year has passed since the World Health Organization declared the coronavirus disease (COVID-19) pandemic on March 11, 2020 [1]. Although there has been extensive research on the acute phase of the disease, limited studies have investigated its long-term health effects [2–6]. Regarding intensive care unit (ICU)-treated patients, there is a need to evaluate the occurrence of post-intensive care syndrome (PICS) [7] because it has become recognized and is the next care target in the field of critical care medicine [8–10].

PICS is defined as a new or worsening impairment in physical, mental, or cognitive health status that arises and persists after hospitalization for critical illness [7]. Although there have been recent reports regarding long-term consequences, including fatigue, insomnia, and anxiety or depression, among COVID-19 survivors at or 6 months after acute infection, information regarding critically ill patients remains missing [2, 5, 6]. Small-scale studies investigating ICU treated patients with COVID-19 have suggested that respiratory, mobility, and cognitive consequences are common at approximately a month after hospital discharge [3, 6]. However, PICS occurrence in COVID-19 survivors remains largely unclear. There is a need to evaluate long-term PICS occurrence in this population with respect to all three PICS components.

This study aimed to investigate the full spectrum of PICS, including its physical, mental, and cognitive aspects, in COVID-19 survivors hospitalized at our single-center ICU.

Study design and subjects

This prospective study enrolled critically ill patients with COVID-19 who were consecutively hospitalized in the ICU of a single institution in central Tokyo, Japan between March 19 and April 30, 2020. The hospital provided permission for collecting data from electronic health records; moreover, this study was approved by the institutional review board (approval number 20-R102).

The inclusion criteria included ICU admission and laboratory or radiological confirmation of COVID-19 [11]. We excluded patients who died during hospitalization. A laboratory diagnosis was based on positive reverse-transcriptase polymerase chain reaction test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using samples such as nasal swabs, pharyngeal swabs, or sputum [12]. A radiological COVID-19 diagnosis was based on the presence of bilateral ground-glass opacities on chest computed tomography [13].

Questionnaire details

A telephone call was made to each patient by a team of doctors, nurses, and a physical therapist who were all ICU staff members. First, the patient’s ability to complete the mailed questionnaire was assessed. In the case of severe mental distress or patient refusal, the questionnaire was not mailed. The survey comprised the following items: the post-COVID-19 functional status (PCFS) scale [14], modified medical research council dyspnea scale (mMRC) [15], impact of event scale-revised (IES-R) [16], and hospital anxiety and depression scale (HADS) [17]. Additionally, the participants were asked about changes in living or working status; moreover, they conducted self-assessments of their concentration, memory, and forgetfulness (Additional file 1). The survey booklet and an informed consent form were sent to the patients’ homes in mid-August 2020. Responses from patients with valid consent documents were used for assessment. A second survey with similar questions was sent to consenting patients in mid-October 2020.

Data collection

We collected information regarding baseline characteristics, comorbidities, illness severity, mortality prediction scores (Sequential Organ Failure Assessment [SOFA] score, Acute Physiology and Chronic Health Evaluation [APACHE] II and III scores, Simplified Acute Physiology Score [SAPS II]), ICU therapies (systemic steroids, invasive mechanical ventilation, extracorporeal membrane oxygenation, renal replacement therapy, and continuous benzodiazepine administration), and clinical outcomes. Information regarding delirium was collected from electronic ICU charts. ICU nurses performed routine assessments using the confusion assessment method for the ICU to determine delirium occurrence. Additionally, delirium was defined based on a positive Richmond agitation and sedation scale score [8, 18] or bedside nurse’s judgment of the presence of agitation, hallucination, or dangerous behavior. Moreover, outcomes such as the duration of ICU stay, hospital stay, and place of discharge were investigated.

Study endpoints

The following PICS components were assessed: physical PICS, mental PICS, and cognitive PICS. Physical PICS was defined by a PCFS or mMRC score ≥ 1 [2, 19]. Mental PICS was assessed using IES-R and HADS scores. An IES-R score ≥ 25 indicated post-traumatic stress disorder (PTSD) [16], while scores ≥ 8 for the anxiety and depression components of the HADS survey indicated anxiety and depression, respectively [17]. A composite endpoint of these score results was considered as mental PICS. Cognitive PICS was defined if the patient had complaints of deteriorated concentration, memory, or forgetfulness. Care was offered to patients with positive results for PICS.

Statistical analysis

Each subgroup of patients with PICS was compared with the corresponding non-PICS groups. Specifically, we compared the following variables: baseline demographics, comorbidities, living and marital status, illness severity and mortality prediction scores, ICU treatments, delirium occurrence, and outcomes.

Continuous variables are presented as median and interquartile ranges. Categorical variables are presented as the number and percentages. Between-group comparisons of continuous variables were performed using the Kruskal–Wallis test or Mann–Whitney U-test; moreover, categorical variables were compared using Fisher’s exact test or chi-square test, as appropriate. Statistical analyses were performed using the JMP version 12 statistical software (SAS Institute, Cary, NC, USA). Statistical significance was set at a two-sided p-value < 0.05. Missing data were not replaced or estimated.

Among 27 eligible patients, 20 patients responded with a valid consent form and were included in the initial analysis. The second survey, which was sent 6 months after ICU discharge, was completed by 15 patients who were included in the subsequent assessment (Fig. 1).

Baseline characteristics

Table 1 presents the baseline and demographic characteristics. All patients were of Japanese ethnicity. The median age was 57.5 (interquartile range: 48.8, 71.3) years; moreover, 80% and 85% of participants were male and had comorbidities, respectively. At the time of hospital admission, 80% and 20% of patients were employed/self-employed and unemployed/retired, respectively. Additionally, 55% of patients were married, while 2 (10%) patients were widowed. None of the patients lived in nursing homes or long-term care facilities before hospitalization. All patients were physically independent in daily life activities and none were receiving social services. No patients were previously diagnosed with mental diseases or cognitive impairments.

Table 1

Baseline and demographic characteristics on hospital admission
Age, median (IQR), years	57.5 (48.8, 71.3)
Male, n. (%)	16 (80)
BMI, median (IQR), kg/m²	24.4 (22.0, 28.7)
Overweight (25 ≤ BMI < 35), n (%)	7 (35)
Obese (35 ≤ BMI), n (%)	1 (5)
Comorbidities
Hypertension, n (%)	9 (45)
Diabetes, n (%)	8 (40)
Coronary artery disease, n (%)	1 (5)
Asthma, n (%)	6 (30)
Chronic obstructive pulmonary disease, n (%)	2 (10)
Cancer*, n (%)	1 (5)
Current or former smoker, n (%)	14 (70)
Habitual or occasional alcohol consumption, n (%)	10 (50)
Marital Status
Married	11 (55)
Separated or divorced	0 (0)
Widowed	2 (10)
Unmarried	6 (30)
Unknown	1 (5)
Living Status
Alone	10 (50)
With family	10 (50)
Data are expressed as numbers (percentage) or median (interquartile range).
*Includes untreated or simultaneously treated neoplasms.
IQR, interquartile range; BMI, body mass index

Results of the questionnaire

Table 2 presents the major results of the questionnaire at 4 and 6 months after ICU discharge. At 4 months after ICU discharge, 61% and 71% of patients had PCFS and mMRC scores ≥ 1, respectively. PTSD, anxiety, and depression were observed in 35%, 45%, and 30% of patients, respectively. Moreover, 50%, 40%, and 35% of patients complained of deteriorated concentration, memory, and forgetfulness, respectively. At 6 months, more patients had a PCFS score of 0 (4 months vs. 6 months: 39% vs. 53%); moreover, less patients had PTSD (4 months vs. 6 months: 35% vs. 20%) or deteriorated concentration [4 months vs. 6 months: 50% vs. 13%).

Table 2

Evaluation of physical, mental, and cognitive PICS 4 and 6 months post-ICU discharge
	4 months	6 months
Physical PICS Components
PCFS
0, n (%)	7 (39)	8 (53)
1, n (%)	7 (39)	4 (27)
2, n (%)	3 (17)	2 (13)
3, n (%)	0 (0)	0 (0)
4, n (%)	1 (6)	1 (7)
mMRC
0, n (%)	5 (30)	5 (33)
1, n (%)	9 (53)	7 (47)
2, n (%)	1 (6)	2 (13)
3, n (%)	1 (6)	0 (0)
4, n (%)	1 (6)	1 (7)
Mental PICS Components
IES-R
Median (IQR)	7.5 (4, 26.5)	9 (2, 20.5)
≥ 25, n(%)	7 (35)	3 (20)
HADS
Anxiety
Median (IQR)	6.5 (1.75, 8)	3 (1, 6)
≥ 8, n (%)	9 (45)	3 (20)
Depression
Median (IQR)	7 (3, 8.5)	5 (2.5, 9.5)
≥ 8, n (%)	6 (30)	6 (40)
Cognitive PICS Components
Deterioration in concentration
Yes, n (%)	10 (50)	2 (13)
No, n (%)	8 (40)	7 (47)
Neither, n (%)	2 (10)	5 (33)
Improved since last survey, n (%)		1 (7)
Deterioration in memory
Yes, n (%)	8 (40)	3 (20)
No, n (%)	9 (45)	6 (40)
Neither, n (%)	3 (15)	5 (33)
Improved since last survey, n (%)		1 (7)
Deterioration in forgetfulness
Yes, n (%)	7 (35)	2 (13)
No, n (%)	8 (40)	6 (40)
Neither, n (%)	5 (25)	6 (40)
Improved since last survey, n (%)		1 (7)
Data are expressed as numbers (percentage) or median (interquartile range).
PICS, post-intensive care syndrome; ICU, intensive care unit; PCFS, post-COVID-19 functional scale; mMRC, modified medical research council dyspnea scale; IES-R, impact of event scale-revised; HADS, hospital anxiety and depression scale

Changes in social status at 4 months

Among 16 (80%) patients who were employed or self-employed, 12 fully recovered their pre-hospitalization working status. The remaining 4 patients partially recovered; moreover, all patients recovered or none were unemployed. All patients, except one patient who was discharged to a long-term care hospital, returned to their previous living status at 4 months after ICU discharge.

Occurrence of each PICS component

Figure 2 shows the distribution of patients based on each PICS subgroup. Physical, mental, and cognitive PICS occurred in 14 (78%), 9 (45%), and 11 (55%) patients, respectively. Nine patients presented with anxiety, PTSD, and depression; specifically, patients with anxiety had PTSD, depression, or both. Regarding the cognitive PICS component, 7 patients claimed deterioration in both concentration and memory and additionally claimed deterioration in forgetfulness. Specifically, all patients who claimed deterioration in forgetfulness also claimed worsening of concentration and memory.

Overall PICS occurrence at 4 months

Figure 3 shows the proportion of patients with physical, mental, and cognitive PICS. Sixteen (80%) patients had at least one PICS type. All 9 (45%) patients with mental PICS had physical PICS. Eight (40%) patients had all PICS components.

Comparison of PICS versus non-PICS

Table 3 presents the comparison of each PICS subgroup and the corresponding non-PICS group. There were no significant differences in the compared variables. However, the use rate of systemic steroids (physical PICS vs. non-physical PICS: 86% vs. 50%, p = 0.2; mental PICS vs. non-mental PICS: 89% vs. 64%, p = 0.32; cognitive PICS vs. non-cognitive PICS, 82% vs. 67%, p = 0.62) and continuous benzodiazepine (physical PICS vs. non-physical PICS: 29% vs. 0%, p = 0.52; mental PICS vs. non-mental PICS: 33% vs. 18%, p = 0.62, cognitive PICS vs. non-cognitive PICS, 36% vs. 11%, p = 0.32) tended to be higher in all the PICS subgroups. The comparison according to each questionnaire is displayed in the Additional File 2.

Table 3

Comparison between PICS subgroups and the corresponding non-PICS subgroup
	Total (20)	Physical PICS (14)	Non-physical PICS (4)	p value	Mental PICS (9)	Non-mental PICS (11)	p value	Cognitive PICS (11)	Non-cognitive PICS (9)	p value
Baseline characteristics
Age, median (IQR), years	57.5 (48.8, 71.3)	57.5 (52.3, 69.5)	48.5 (47.8, 54.5)	0.34	58.0 (51.0, 72.0)	56.0 (48.5, 67.0)	0.97	57.0 (48.5, 66.5)	62.0 (51.0, 71.0)	0.49
Male, n (%)	16 (80)	11 (76)	4 (100)	1	6 (67)	10 (90)	0.28	8 (73)	8 (89)	0.59
BMI, median (IQR), kg/m²	24.4 (22.0, 28.7)	24.5 (22.2, 30.1)	22.8 (21.1, 24.9)	0.34	22.3 (22.0, 28.5)	24.9 (22.2, 27.8)	0.52	24.3 (21.6, 28.9)	24.5 (22.1, 25.6)	0.85
Comorbidities
Respiratory comorbidities*, n (%)	7 (35)	5 (36)	1 (25)	1	4 (44)	3 (27)	0.64	4 (36)	3 (33)	1
Current or former smoker, n (%)	14 (70)	8 (57)	4 (100)	0.26	6 (67)	8 (73)	0.63	8 (73)	6 (67)	1
Lifestyle comorbidities†, n (%)	13 (65)	9 (64)	2 (50)	1	4 (44)	9 (82)	0.16	6 (55)	7 (78)	0.37
Living alone, n (%)	10 (50)	7 (50)	1 (25)	0.59	4 (44)	6 (55)	1	5 (45)	5 (56)	1
Married, n (%)	11 (55)	8 (57)	2 (50)	1	6 (67)	5 (45)	0.41	8 (73)	3 (33)	0.17
ICU scores, treatments and events
SOFA, median (IQR)	6.0 (3.0, 8.0)	5.0 (3.0, 7.0)	7.0 (5.8, 8.0)	0.28	6.0 (4.0, 7.0)	6.0 (3.0, 8.0)	0.94	6.0 (4.0, 7.5)	5.0 (3.0, 8.0)	0.88
APACHE-II, median (IQR)	18.0 (12.5, 20.5)	18.0 (11.5, 21.5)	13.0 (12.0, 14.3)	0.26	18.0 (13.0, 19.0)	18.0 (12.0, 22.0)	0.67	13.0 (10.0, 18.5)	19.0 (18.0, 22.0)	0.08
APACHE-III, median (IQR)	52.0 (40.0, 82.0)	52.0 (40.0, 79.0)	42.0 (39.3, 54.5)	0.53	46.0 (40.0, 79.0)	64.0 (44.0, 82.5)	0.41	43.0 (37.8, 72.3)	73.0 (44.0, 83.0)	0.16
SAPS-II, median (IQR)	31.0 (21.5, 42.5)	31.0 (20.0, 46.0)	28.0 (24.5, 32.3)	0.78	31.0 (20.0, 46.0)	30.5 (26.3, 38.8)	0.77	28.5 (20.8, 42.5)	31.0 (27.0, 39.0)	0.6
Invasive mechanical ventilation, n (%)	16 (80)	11 (79)	4 (100)	1	7 (78)	9 (82)	1	10 (90)	6 (67)	0.28
Days of invasive mechanical ventilation, median (IQR), days	5.0 (3.8, 8.3)	5.0 (3.5, 16.5)	5.5 (4.8, 6.3)	0.9	7.0 (3, 16.5)	5.0 (4.0, 6.0)	0.79	7.0 (3.3, 18.8)	5.0 (4.3, 5.0)	0.32
Extracorporeal membrane oxygenation, n (%)	1 (5)	1 (7)	0 (0)	1	0 (0)	1 (9)	1	1 (9)	0 (0)	1
Tracheostomy, n (%)	3 (15)	3 (21)	0 (0)	1	2 (22)	1 (9)	0.57	3 (27)	0 (0)	0.22
Renal replacement therapy, n (%)	1 (5)	1 (7)	0 (0)	1	0 (0)	1 (9)	1	0 (0)	1 (11)	0.45
Systemic steroids, n (%)	15 (75)	12 (86)	2 (50)	0.2	8 (89)	7 (64)	0.32	9 (82)	6 (67)	0.62
Continuous benzodiazepine, n (%)	5 (25)	4 (29)	0 (0)	0.52	3 (33)	2 (18)	0.62	4 (36)	1 (11)	0.32
Occurrence of delirium, n (%)	8 (40)	6 (43)	2 (50)	0.09	4 (44)	4 (36)	0.36	6 (55)	2 (22)	0.2
Outcomes
ICU stay, median (IQR), days	6.0 (4.0, 11.5)	6.5 (5.0, 14.5)	6.0 (5.5, 6.8)	0.56	7.0 (4.0, 13.0)	6.0 (4.5, 7.5)	0.62	9.0 (5.0, 17.5)	5.0 (4.0, 6.0)	0.1
Hospital stay, median (IQR), days	21.0 (17.8, 36.5)	24.5 (18.3, 39.5)	18.5 (17.5, 20.3)	0.26	19.0 (18.0, 33.0)	24.0 (17.0, 38.0)	0.88	19.0 (18.0, 43.5)	24.0 (15.0, 35.0)	0.68
Discharged to other hospital or recovery hotel^‡, n (%)	4 (20)	4 (29)	0 (0)	0.52	3 (33)	1 (9)	0.28	4 (36)	0 (0)	0.09
Data are expressed as numbers (percentage), or median (interquartile range).
*Includes chronic respiratory disease and asthma.
†Includes hypertension, diabetes mellitus, dyslipidemia, and obesity.
‡Patients who had repeated positive reverse-transcriptase polymerase chain reaction tests required isolation at an observatory hotel before discharge.

Summary of findings

This single-center study investigated PICS occurrence in 20 patients who were hospitalized in the ICU for severe COVID-19 during the first wave of the pandemic in Tokyo. At 4 months after ICU discharge, the occurrence rates of physical, mental, and cognitive PICS were 78%, 45%, and 55%, respectively. Moreover, 80% and 40% of patients had at least one and all PICS components, respectively. At 6 months after ICU discharge, there was an improvement tendency in most questionnaire scores.

Comparison with other studies

To our knowledge, this is the first study to examine the long-term outcomes (PICS occurrence) among COVID-19 survivors. Martillo et al. investigated COVID-19 survivors of the ICU at 1 month from hospital discharge to discover a 91% prevalence of overall PICS, which was predominated by physical impairments seen in 87% of the patients[6]. Mental and cognitive impairments were seen in 22% and 8% respectively. The overall prevalence of PICS and physical impairments was higher than our study, which may be because patients were evaluated briefly after hospital discharge. In contrast, three previous studies have investigated all three PICS components in a non-COVID population after at least 3 months of discharge. All three studies used different methods to assess each component. In these previous studies, physical impairments were investigated using the physical components of the 36-item Short Form (SF-36) [8], Katz Index of Independence in Activities of Daily Living [20], and Euro-QOL [21], with reported prevalence rates of 31%, 23%, and 42%, respectively. In the present study, we used the mMRC and PCFS since the mMRC is appropriate for assessing post-COVID breathing problems [2]; moreover, PCFS is valid for assessing mobility and the capability of usual activities [19]. Regarding the mental component, the SF-36 [8], Beck Depression Inventory-II [20], and combination of HADS and Post-Traumatic Stress Symptom-10 [21] were used, with prevalence rates of 15%, 33%, and 58%, respectively. We used the HADS and IES-R, which conform to the consensus of the Society of Critical Care Medicine [22] The use of HADS was consistent with the study by Maley et al. [21]; moreover, it may have attributed to the comparable occurrence rates of mental PICS. Finally, cognitive impairment was assessed using the Short Memory Questionnaire [8], Repeatable Battery for the Assessment of Neuropsychological Status [20], and self-assessment questions [21], with prevalence rates of 37%, 37%, and 56%, respectively.

Among the three studies, the occurrence of at least one PICS domain ranged from 64–84%; moreover, the rates of having all three PICS types were 2%, 6%, and 33% in each study [7, 19, 20]. Our occurrence rates were most comparable with those reported by Maley et al. who studied the youngest patients (mean age: 59 years) and used the HADS and self-assessment questions for assessing mental and cognitive impairments [21]. Kawakami et al. reported a lower prevalence, which could be attributed to the authors comparing SF-36 scores with baseline scores that were reported by patients’ proxy recalling the status at 4 weeks before the acute illness. Additionally, Marra et al. excluded patients with preexisting physical, mental, and cognitive impairments, which could explain the lower PICS frequency. Contrastingly, our findings were based on one-point evaluation. However, none of our included patients had preexisting physical, mental, or cognitive impairments; moreover, the evaluations employed were suitable for assessing long-term consequences in ICU-treated COVID-19 survivors.

Mechanisms

The observed high PICS prevalence in COVID-19 survivors could be attributed to several reasons. First, we only included COVID-19 survivors. The included patients were overall younger than the general ICU-treated population [8, 23, 24]; moreover, patients with PICS impairments tended to use systemic steroids or benzodiazepines, which are known factors for mental and physical PICS [25]. Additionally, long-term health effects across all severities have been recognized in numerous COVID-19 survivors [2, 3]. Second, our patients were victims of a new and obscure disease and also a phenomenal pandemic. Media influence and COVID-19-related celebrity deaths may have triggered mental impairments in our patients [26]. Finally, our results were based on one-point evaluations and were not compared to the baseline status, which could have led to a higher prevalence.

Clinical implementations

We observed a high prevalence rate of PICS in COVID-19 survivors, which indicates the importance of acute follow-up for ICU patients. Our patients showed various long-term consequences; therefore, there is a need to evaluate all three domains to allow comprehensive care. Furthermore, although we did not observe significant differences, there were tendencies of more frequent use of systemic steroids and continuous benzodiazepine in each PICS subgroup compared with the corresponding non-PICS groups.

Given that the aforementioned drugs are known risk factors for PICS [25], physicians should acknowledge their long-term disadvantages in patients. Moreover, substituting either drug for another may be considered [27]. For instance, while steroid administration for COVID-19 is controversial, most studies have favored using interleukin-6 (IL-6) inhibitors [28]. Additionally, there is accumulating evidence regarding the effectiveness of anti-tumor necrosis factor (TNF) therapy for COVID-19 [29]. There is a need for more studies on both IL-6 and TNF inhibitors and their role in COVID-19; however, they may be an alternative for steroids and also protect against PICS development.

Limitations

This study had several limitations. First, this study was conducted by the ICU staff; therefore, 1- or 3-month post-ICU evaluation could not be performed owing to the heavy workload persistent during the pandemic. Second, we could not perform comparisons with the baseline status. Third, selection bias may have occurred since this was a mailed survey requiring responses from participants. Patients with severe impairments or illness were less likely to provide consent or responses to the survey. Fourth, this study had a small sample size and the 6-month survey response rate was low. Fifth, we could not perform statistical comparisons between the 4- and 6-month questionnaire results. Finally, the PICS definition remains unclear; moreover, our evaluation methods were limited to questionnaires answerable via postal mail. However, the mMRC was used in accordance with the study by Huang et al. [2]; furthermore, the PCFS is appropriate for physical PICS examination since it is mainly associated with the capability of mobility and usual activities [19]. Additionally, the usage of HADS and IES-R conformed with the consensus of the Society of Critical Care Medicine for evaluating mental PICS [22]. Our most significant limitation was that the evaluation of the cognitive component relied on self-assessment.

The rate of PICS among COVID-19 survivors was as high as 80%; moreover, the co-occurrence of all 3 domains was observed in 40% of patients. Long-term and comprehensive evaluation of all three PICS components is crucial for these patients to provide appropriate care.

APACHE: Acute physiology and chronic health evaluation

BMI: Body mass index

COVID-19: Coronavirus disease

HADS: Hospital anxiety and depression scale

IES-R: Impact of event scale-revised

ICU: Intensive care unit

IL-6: Interleukin-6

mMRC: Modified medical research council dyspnea scale

PCFS: Post-COVID-19 functional status scale

PICS: Post-intensive care syndrome

PTSD: Post-traumatic stress disorder

SAPS: Simplified acute physiology score

SARS-CoV-2: Severe acute respiratory syndrome coronavirus-2

SF-36: 36-item Short Form

SOFA: Sequential organ failure assessment

TNF: Tumor necrosis factor

Ethics approval and consent to participate

Permission to recruit patients was provided from the hospital; further, this study was approved by the institutional review board (approval number 20-R102). A consent form was sent and retrieved from all participants.

Consent for publication

Not applicable

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This study was supported by the Daiwa Securities Health Foundation.

Authors' contributions

AB, TH, YT and SI were responsible for the study concept and design. AB and TH wrote the manuscript. MS performed the statistical analysis. AB, YT, AS, SS, MS, and SI collected patient information. YM was responsible for patient follow-up. SI, KA, NO, and SI contributed to reviewing and proofreading the manuscript. All authors read and approved the final manuscript.

Correspondence

The corresponding author is Toru Hifumi.

Acknowledgements

We appreciate Atsushi Sekimori for collecting data and patient information. We thank all members of the Department of Emergency Medicine and Critical Care, Department of Intensive Care, and staff members of the ICU.

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AdditionalFile1.docx
Additional file 1. File format: .docx Title of data: English translation of the cognitive component of the questionnaire
Tableadditional.xlsx
Additional file 2. Comparison of patients according to each questionnaire results File format: .xlsx Title of data: Comparison of patients according to each questionnaire results

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Post-Intensive Care Syndrome Associated With Coronavirus Disease: A Single Institutional Study In Tokyo

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Abstract

Figures

Background

Methods

Study design and subjects

Questionnaire details

Data collection

Study endpoints

Statistical analysis

Results

Baseline characteristics

Results of the questionnaire

Changes in social status at 4 months

Occurrence of each PICS component

Overall PICS occurrence at 4 months

Comparison of PICS versus non-PICS

Discussion

Summary of findings

Comparison with other studies

Mechanisms

Clinical implementations

Limitations

Conclusions

Abbreviations

Declarations

References

Supplementary Files

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