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Original Article
Predicting factors associated with prolonged intensive care unit stay of patients with COVID-19
Won Ho Han1,2orcid, Jae Hoon Lee1,2orcid, June Young Chun3orcid, Young Ju Choi3orcid, Youseok Kim1,4orcid, Mira Han5orcid, Jee Hee Kim1,4orcid
Acute and Critical Care 2023;38(1):41-48.
Published online: February 22, 2023
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1Department of Critical Care Medicine, National Cancer Center, Goyang, Korea

2Department of Surgery, National Cancer Center, Goyang, Korea

3Department of Internal Medicine, National Cancer Center, Goyang, Korea

4Department of Anesthesiology, National Cancer Center, Goyang, Korea

5Biostatistics Collaboration Team, National Cancer Center, Goyang, Korea

Corresponding author: Jee Hee Kim Department of Critical Care Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel +82-31-920-1400 Fax +82-31-920-1400 Email:
• Received: September 28, 2022   • Revised: November 17, 2022   • Accepted: November 21, 2022

Copyright © 2023 The Korean Society of Critical Care Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • Background
    Predicting the length of stay (LOS) for coronavirus disease 2019 (COVID-19) patients in the intensive care unit (ICU) is essential for efficient use of ICU resources. We analyzed the clinical characteristics of patients with severe COVID-19 based on their clinical care and determined the predictive factors associated with prolonged LOS.
  • Methods
    We included 96 COVID-19 patients who received oxygen therapy at a high-flow nasal cannula level or above after ICU admission during March 2021 to February 2022. The demographic characteristics at the time of ICU admission and results of severity analysis (Sequential Organ Failure Assessment [SOFA], Acute Physiology and Chronic Health Evaluation [APACHE] II), blood tests, and ICU treatments were analyzed using a logistic regression model. Additionally, blood tests (C-reactive protein, D-dimer, and the PaO2 to FiO2 ratio [P/F ratio]) were performed on days 3 and 5 of ICU admission to identify factors associated with prolonged LOS.
  • Results
    Univariable analyses showed statistically significant results for SOFA score at the time of ICU admission, C-reactive protein level, high-dose steroids, mechanical ventilation (MV) care, continuous renal replacement therapy, extracorporeal membrane oxygenation, and prone position. Multivariable analysis showed that MV care and P/F ratio on hospital day 5 were independent factors for prolonged ICU LOS. For D-dimer, no significant variation was observed at admission; however, after days 3 and 5 days of admission, significant between-group variation was detected.
  • Conclusions
    MV care and P/F ratio on hospital day 5 are independent factors that can predict prolonged LOS for COVID-19 patients.
▪ Predicting the length of stay of intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19) is essential for efficient use of ICU resources.
▪ Mechanical ventilator care and the ratio of arterial oxygen partial pressure to fractional inspired oxygen on hospital day 5 are independent factors that can predict prolonged length of stay for COVID-19 patients.

In 2020, the World Health Organization declared a pandemic state for the coronavirus disease 2019 (COVID-19) after a steep increase in the number of infected patients worldwide, including South Korea [1]. Most patients recover after experiencing mild symptoms accompanied by upper respiratory tract infection; however, approximately 10%–15% of patients require oxygen supply, and approximately 5% are classified as severe patients that require high-flow nasal cannula (HFNC) oxygen delivery, mechanical ventilation (MV), and extracorporeal membrane oxygenation (ECMO) in the intensive care unit (ICU) [2,3].
Medical resources, including ICUs, were prepared around the world in the event of pandemic spread and severe disease. Moreover, studies have reported that during the 2009 H1N1 pandemic, patients’ underlying disease and disease progression, economic status of the pandemic region, and regional characteristics affected mortality [4]. Likewise, during the COVID-19 pandemic, after 2020, mortality varied according to ICU resources in each country [5,6]. However, even in countries or regions that are relatively well prepared for medical emergencies, the steep increase in ICU patients during the pandemic and consequent saturation of resources and overloading of medical staff was associated with a rise in mortality from 28.1% to 65.7% [7,8].
For instance, in South Korea, the number of COVID-19 patients rapidly increased after June 2021 with the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant. Yet, the number of severe patients was below 200 until June 2021, and then increased to approximately 1,000 at the peak of the outbreak in December 2021. Although mortality remained below 0.2% before the outbreak based on disinfection policies, vaccination, and sufficient medical resources, it increased to 1% on average by December 2021, suggesting that efficient use of ICU resources, including medical instruments and staff, significantly impacted mortality during pandemic conditions [9,10].
To ensure that ICU resources are efficiently distributed, it is necessary to predict the length of stay (LOS) of COVID-19 ICU patients by analyzing disease progression and assessing severity [11,12]. This relationship remains controversial and needs to be clarified in future research, and several studies have shown that the clinical features of COVID-19 differ from acute respiratory distress syndrome (ARDS) [13,14]. Therefore, this study analyzed the clinical characteristics of patients with severe COVID-19 based on their clinical care and identified the predictive factors associated with prolonged ICU LOS of 2 weeks or longer.
This study was approved by the Institutional Review Board of the National Cancer Center (No. NCC 2022–0215). Informed consent was waived in accordance with the Institutional Review Board due to the retrospective nature of this study.
Study Design and Patients
This retrospective study was conducted at a single center. The participants were patients admitted to the ICU due to COVID-19 infection between March 2021 and February 2022. The center had eight beds in the ICU for patients with severe COVID-19 since March 2021. Among the severe COVID-19 patients in the ICU, those who showed a low probability of pneumonia related to COVID-19 infection (bacterial pneumonia, malignancy) among those who received oxygen therapy at the HFNC level or above were excluded through medical review (Figure 1).
ICU admission and discharge criteria for all patients included in this study were defined in accordance with government quarantine policies. All patients admitted to the ICU were administered oxygen therapy at the HFNC level or above at the time of admission; MV or ECMO was applied depending on the stage of pneumonia and ARDS. Additionally, all patients were treated according to the clinical practice guidelines for ARDS and the Sepsis-Surviving Campaign guidelines [15,16]. Treatment included administering remdesivir and steroids, as well as antibiotics and anticoagulants, to prevent secondary bacterial pneumonia. For steroid therapy, 6 mg dexamethasone was administered once a day for 10 days. For ARDS aggravation, despite steroid therapy, dosage was increased to 20 mg once a day for 5 days, with tapering depending on patient status [17]. Tocilizumab 8mg/kg was administered when the oxygen demand increased within 24–48 hours and C-reactive protein (CRP) level was ≥5.0 mg/dL even after starting steroid administration [18]. When the patient showed a decrease in oxygen requirement following ICU care, treatment was switched to a 4 L/min nasal prong. Patients were transferred to the general ward when they were deemed stable based on clinical symptoms, blood test results, and X-ray results. However, considering the possibility of further deterioration, some cases were transferred after 1–2 days of follow-up observation at the discretion of the attending physician.
Data Collection
To identify the factors associated with prolonged ICU LOS ≥2 weeks, patient age, sex, body weight, underlying disease, and smoking history were investigated. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were determined immediately after hospitalization to assess severity. Following ICU admission, blood test results (neutrophil-lymphocyte ratio (NLR), CRP level, D-dimer level, and PaO2 to FiO2 ratio (P/F ratio) on days 3 and 5 of admission were compared to analyze the association between prolonged ICU LOS and changes in blood parameters.
Statistical Analyses
Patient characteristics and laboratory results were summarized as frequencies with percentages for categorical variables. Normality was assessed using the Shapiro-Wilk test. If the assumption of normality was satisfied, continuous variables were presented as mean±standard deviation, and a t-test was used. If the normality assumption was not satisfied, continuous variables were presented as median (range) and the Wilcoxon rank-sum test was used. A logistic regression model was used to identify the prognostic factors associated with a prolonged ICU stay. In the multivariable logistic model, we included all risk factors for prolonged ICU stay with a P-value <0.05, and a risk factor for prolonged ICU stay was selected using backward elimination in the final model. All analyses were performed using SAS software ver. 9.4 (SAS institute).
Patient Characteristics
A total of 118 patients were admitted to the COVID-19-designated ICU, and 96 patients were included in the study after excluding those who did not meet the study criteria (Figure 1). After HFNC treatment, 65 patients showed improvement, while 31 received MV care. Most MV care (28/31, 90%) and continuous renal replacement therapy (CRRT) were performed within 3 days of initial admission. ECMO was performed in five cases on admission to the ICU, and for the remaining three cases, ECMO treatment was applied due to ARDS exacerbation even after 5–10 days of MV care. A neuromuscular (NM) blocking agent was injected in 61.2% (19/31) of patients who received MV care, while 32.3% (10/31) were placed in a prone position. Eight patients (8.3%) showed ARDS aggravation despite MV care, and ECMO was applied. Twenty-three patients (24%) received treatment in the ICU for 2 weeks or more. Of the 96 patients, four died in the ICU due to sepsis from pneumonia aggravation (n=3) and pulmonary hemorrhage during ECMO for ARDS (n=1). All four deceased patients died after being in the ICU for more than 2 weeks. The median ICU LOS was 14 days as a cut off for prolonged ICU LOS (Table 1).
Tracheostomy was performed on nine patients. Of these, seven underwent tracheostomy after undergoing ECMO treatment and two patients due to prolonged intubation (more than 2 weeks). Tracheostomy was performed by an otolaryngologist in the ICU by an open method.
Predicting Factors for Prolonged ICU LOS
Univariable analyses showed that SOFA score at the time of ICU admission, CRP level, high-dose steroids, MV care, CRRT, ECMO, and prone position was significantly correlated (Table 2) with ≥2 weeks of ICU care (prolonged ICU stay). Multivariable analysis showed that MV care and P/F ratio on hospital day 5 were independent factors for prolonged ICU LOS (Table 3).
Laboratory Tests Associated with Prolonged ICU LOS
CRP level showed a decrease between days 3 and 5 in both groups, but D-dimer showed a decrease only in the non-ICU LOS group with LOS <2 weeks. The P/F ratio showed an increase between days 3 and 5 in both groups. CRP level was significantly higher in the prolonged ICU LOS patients at 6.2 mg/dl (range, 0.1–19.1) vs. 13.4 mg/dL (range, 1.8–25.6) (P=0.029) at the time of ICU admission; however, the level was reduced on hospital days 3 and 5. For the D-dimer level, no significant variation was observed at ICU admission; however, after days 3 and 5, significant between-group variation was detected (1.0 [range, 0.2–20.0] vs. 3.2 [range, 0.3–20.0], P=0.007). Finally, for the P/F ratio, an increasing trend was observed in the non–ICU LOS group with LOS <2 weeks on days 3, but no significant difference was observed, and after 5 days a significant difference between the two groups was noted (158.6 [range, 75.6–433.3] vs. 121.6 [range, 55.9–255.0], P=0.001) (Table 4).
Medications for Mechanical Ventilator Care Patients
For MV care, dexmedetomidine was preferentially administered as a sedative, and midazolam or propofol was added when additional deep sedation was required during the first few days of MV care according to the attending physician’s discretion. Administration of midazolam (38.5% vs 94.4%, P=0.001) and NM blocking agent (38.5% vs 77.8%, P=0.027) was significantly associated with prolonged ICU LOS. Duration of sedative use (3 [2–5] vs. 7 [3–12], P=0.030) and NM blocking agents (2 [1–3] vs. 6 [4–9], P=0.011) were also statistically significant with prolonged ICU LOS (Table 5).
To ensure the appropriate distribution of medical resources and efficient treatments, it is important to determine the current status of medical resource use. During a pandemic, a high burden of patients requiring intensive care is associated with ICU mortality, which places a special emphasis on ICU management [19]. Most previous studies have reported on COVID-19 patient mortality and the risk factors for ICU admission; however, only a few studies have investigated the factors that influence ICU LOS. In this study, the predictive factors associated with prolonged ICU LOS (≥2 weeks) were examined, and MV care alone was observed to be an independent factor, while an increase in the D-dimer level after days 3 and 5 of ICU admission was shown to be significantly correlated with ICU admission.
Age, underlying disease, smoking history, body mass index, APACHE II, and SOFA scores are well-known clinical factors associated with COVID-19 prognosis [20-22]. However, in this study, MV care was the only factor that significantly impacted ICU LOS. MV care is one of the most important treatments for ARDS due to COVID-19, which has been reported to necessitate a greater level of deep sedation than ARDS from other causes [23,24]. Moreover, deep sedation can delay MV weaning and induce muscle weakness and exercise intolerance. Similarly, in this study, midazolam and a NM blocking agent were used to deeply sedate numerous patients, which is presumably why MV care had a greater impact on ICU LOS than any other factor.
Previous studies have reported that CRP and D-dimer levels and NLR and P/F ratios predict the severity and prognosis of COVID-19 patients [25-27]. In this study, the blood parameters measured at the time of ICU admission did not show significant between-group variations while D-dimer levels showed an increasing trend in the prolonged ICU LOS group. Progression of COVID-19 infection is correlated with coagulopathy. Because the D-dimer test is sensitive to measuring coagulopathy, analyzing its dynamic changes may serve as a predictor of prolonged ICU LOS [28,29].
A limitation of this study is that it was conducted as a small-scale, single-center study. Additionally, as a retrospective study, some variables that affect ICU LOS could not be analyzed at the same time points. Also, factors such as nutritional status and sarcopenia that were reported in other studies to influence ICU LOS could not be included. Future studies should investigate ways to reduce MV care duration for ICU rehabilitation, early MV weaning, and nutritional support to reduce ICU LOS and mortality.
MV care and P/F ratio on hospital day 5 are independent factors that predict prolonged ICU LOS in COVID-19 patients. Further studies should investigate ways to reduce MV care duration to reduce ICU LOS.


No potential conflicts of interest relevant to this article are reported.








Conceptualization: JHK. Data curation: WHH, JHL, JYC, YJC, YK. Formal analysis: MH. Methodology: JHL. Project administration: JHK. Visualization: WHH. Writing–original draft: WHH. Writing–review & editing: JYC, YJC, YK. All authors read and approved the final manuscript.

Figure 1.
Flowchart of the study. COVID-19: coronavirus disease 2019; ICU: intensive care unit.
Table 1.
Patient characteristics
Variable Value (n=96)
 Male 54 (56.3)
 Female 42 (43.8)
Age (yr) 64.9±12.6
Body mass index (kg/m2) 25.1±3.6
Underlying disease
 Diabetes mellitus 24 (25.0)
 Hypertension 51 (53.1)
 Chronic obstructive pulmonary disease 6 (6.3)
 Cardiovascular disease 16 (16.7)
 Chronic kidney disease 4 (4.2)
Smoking 32 (33.3)
From diagnosis to ICU admission (day) 5.5 (0.0–23.0)
APACHE II score 28.0 (15.0–55.0)
SOFA score 4.0 (3.0–13.0)
Initial Lab
 NLR 8.8 (1.6–59.4)
 D-dimer (μg/ml) 1.4 (0.2–20.0)
 C-reactive protein (mg/dl) 7.3 (0.1–25.6)
 P/F ratio 108.8 (43.6–510.0)
Steroid therapy
 Standard dose 49 (51.0)
 High dosea) 47 (49.0)
Tocilizumab 24 (25.0)
Ventilator care 31 (32.3)
CRRT 5 (5.2)
ECMO 8 (8.3)
Prone position 17 (17.7)
ICU stay of length (day) 14 (6–18)
 <2 wk 73 (76.0)
 ≥2 wk 23 (24.0)
 Survival 92 (95.8)
 Mortality 4 (4.2)

Values are presented as number (%), mean±standard deviation, or median (range).

ICU: intensive care unit; APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment; NLR: neutrophil-lymphocyte ratio; P/F ratio: PaO2 to FiO2 ratio; CRRT: continuous renal replacement therapy; ECMO: extracorporeal membrane oxygenation.

a) High dose: 20 mg dexamethasone was administered once a day for 5 days.

Table 2.
Univariable analysis for prolonged ICU length of stay
Variable <2 wk (n=73) ≥2 wk (n=23) P-value
Sex 0.608
 Male 40 (54.8) 14 (60.9)
 Female 33 (45.2) 9 (39.1)
Age (yr) 64.8±13.4 65.0±10.0 0.934
Body mass index (kg/m2) 25.2±3.7 24.9±3.6 0.720
Underlying disease
 Diabetes mellitus 19 (26.0) 5 (21.7) 0.678
 Hypertension 35 (47.9) 16 (69.6) 0.070
 Chronic obstructive pulmonary disease 4 (5.5) 2 (8.7) 0.627
 Cardiovascular disease 10 (13.7) 6 (26.1) 0.201
 Chronic kidney disease 2 (2.7) 2 (8.7) 0.241
Smoking 24 (32.9) 8 (34.8) 0.865
From diagnosis to ICU admission (day) 5.8 (0.0–23.0) 3.9 (0.0–21.0) 0.142
APACHE II score 27.0 (15.0–40.0) 30.0 (18.0–55.0) 0.050
SOFA score 4.0 (3.0–10.0) 5.0 (3.0–13.0) <0.001
Initial lab
 NLR 8.8 (1.6–54.7) 8.9 (1.8–59.4) 0.867
 D-dimer (μg/ml) 1.2 (0.2–20.0) 1.9 (0.5–20.0) 0.070
 C-reactive protein (mg/dl) 6.2 (0.1–19.1) 13.4 (1.8–25.6) 0.029
 P/F ratio 113.3 (43.6–428.3) 100.0 (45.7–510.0) 0.120
Steroid therapy 0.001
 Standard dose 44 (60.3) 5 (21.7)
 High dose 29 (39.7) 18 (78.3)
Tocilizumab 16 (21.9) 8 (34.8) 0.214
Mechanical ventilator 13 (17.8) 18 (78.3) <0.001
CRRT 1 (1.4) 4 (17.4) 0.011
ECMO 1 (1.4) 7 (30.4) <0.001
Prone position 8 (11.0) 9 (39.1) 0.004

Values are presented as number (%), mean±standard deviation, or median (range).

ICU: intensive care unit; APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment; NLR: neutrophil-lymphocyte ratio; P/F ratio: PaO2 to FiO2 ratio; CRRT: continuous renal replacement therapy; ECMO: extracorporeal membrane oxygenation.

Table 3.
Multivariable analysis factors associated with prolonged ICU stay
Variable Univariable analysis
Multivariable analysis (Uni P<0.05)
Multivariable analysis (Backward selection)
OR (95% CI) P-value OR (95% CI) P-value OR (95% CI) P-value
 Male Reference
 Female 0.779 (0.300–2.027) 0.609
Age 1.002 (0.965–1.040) 0.933
Body mass index 0.976 (0.858–1.111) 0.716
 Diabetes mellitus 0.789 (0.258–2.420) 0.679
 Hypertension 2.482 (0.913–6.745) 0.074
 Chronic obstructive pulmonary disease 1.644 (0.281–9.612) 0.581
 Cardiovascular disease 2.224 (0.707–6.988) 0.171
 Chronic kidney disease 3.381 (0.449–25.475) 0.237
Smoking 1.089 (0.406–2.923) 0.865
APACHE II score 1.115 (1.020–1.217) 0.015 0.875 (0.731–1.047) 0.144
SOFA score 1.880 (1.361–2.599) 0.001 1.099 (0.511–2.367) 0.808
Initial Lab
 NLR 1.003 (0.963–1.045) 0.872
 D-dimer (μg/ml) 1.059 (0.969–1.157) 0.204
 C-reactive protein 1.090 (1.014–1.173) 0.020 1.096 (0.970–1.238) 0.142
 P/F ratio 0.997 (0.992–1.002) 0.264
HD 3
 D-dimer (μg/ml) 1.070 (0.994–1.152) 0.072
 C-reactive protein 1.093 (0.994–1.202) 0.065
 P/F ratio 0.993 (0.992–1.002) 0.104
HD 5
 D-dimer (μg/ml) 1.098 (1.010–1.194) 0.027 1.044 (0.886–1.230) 0.606
 C-reactive protein 1.123 (0.975–1.293) 0.109
 P/F ratio 0.986 (0.976–0.996) 0.005 0.980 (0.964–0.997) 0.024 0.984 (0.971–0.996) 0.001
Steroid therapy
 Standard Reference Reference
 High dose 5.461 (1.825–16.340) 0.002 2.549 (0.612–10.615) 0.198
Tocilizumab 1.900 (0.684–5.278) 0.218
Ventilator care 16.615 (5.219–52.902) <0.001 11.521 (1.515–87.618) 0.018 16.338 (5.129–52.045) <0.001
CRRT 15.158 (1.599–143.649) 0.017 4.897 (0.211–113.448) 0.321
ECMO 31.500 (3.618–274.285) 0.001 9.198 (0.213–398.049) 0.248
Prone position 5.223 (1.715–15.909) 0.003 2.635 (0.609–11.395) 0.194

ICU: intensive care unit; OR: odds ratio; CI: confidence interval; APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment; NLR: neutrophil-lymphocyte ratio; P/F ratio: PaO2 to FiO2 ratio; HD: hospital day; CRRT: continuous Renal Replacement Therapy; ECMO: Extracorporeal membrane oxygenation.

Table 4.
Laboratory tests associated prolonged ICU length of stay
Variable <2 wk (n=73) ≥2 wk (n=23) P-value
C-reactive protein (mg/dl)
 Initial 6.2 (0.1–19.1) 13.4 (1.8–25.6) 0.029
 HD 3 3.9 (0.4–18.8) 6.5 (0.4–19.8) 0.046
 HD 5 1.9 (0.2–14.4) 2.2 (0.1–18.4) 0.304
D-dimer (μg/ml)
 Initial 1.2 (0.2–20.0) 1.9 (0.5–20.0) 0.070
 HD 3 1.2 (0.2–20.0) 2.7 (0.4–20.0) 0.013
 HD 5 1.0 (0.2–20.0) 3.2 (0.3–20.0) 0.007
P/F ratio
 Initial 113.3 (43.6–428.3) 100.0 (45.7–510.0) 0.120
 HD 3 139.4 (64.5–636.7) 107.4 (75.1–375.0) 0.053
 HD 5 158.6 (75.6–433.3) 121.6 (55.9–255.0) 0.001

Values are presented as median (range). No laboratory tests were performed in two patients in HD 3 and five patients in HD 5.

ICU: intensive care unit; HD: hospital day; P/F ratio: PaO2 to FiO2 ratio.

Table 5.
Medications for mechanical ventilator care patients
Variable ICU stay
<2 wk (n=13) ≥2 wk (n=18)
 Dexmedetomidine 12 (92.3) 18 (100) 0.419
 Midazolam 5 (38.5) 17 (94.4) 0.001
 Propofol 0 4 (22.2) 0.097
NM blocking agent 5 (38.5) 14 (77.8) 0.027
Duration of using sedatives 3 (2–5) 7 (3–12) 0.030
Duration of using NM blocking agent 2 (1–3) 6 (4–9) 0.011
High-dose steroid 7 (53.8) 14 (77.8) 0.247

Values are presented as number (%) or median (range).

ICU: intensive care unit; NM: neuromuscular

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