J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 13, Number 10-11, November 2021, pages 487-496

Clinical and Laboratory Profile of COVID-19 Pneumonia Patients With a Complicated Post-Intensive Care Unit Hospital Course

Figure 1. Flow chart depicting how the two study groups was obtained. ICU: intensive care unit; COVID-19: coronavirus disease 2019; PCR: polymerase chain reaction; ED: emergency department.

Figure 2. Line graphs juxtaposing the temporal trends of median values of four biomarkers (clockwise from top left: D-dimer, LDH, ferritin, and CRP) in the complicated post-ICU course and uncomplicated post-ICU course groups over the last three ICU days, including the day of ICU exit. Median values on the day of ICU entry are provided as points of reference. ICU: intensive care unit; LDH: lactate dehydrogenase; CRP: C-reactive protein.

Figure 3. Tukey box plots comparing median biomarker levels in the two groups on day of ICU exit. The central rectangle spans the interquartile range (IQR), and the line within the rectangle marks the median. The square symbol marks the mean. The “whiskers” above and below the box are drawn to the furthest point within 1.5 × IQR from the box (the non-outlier range). Asterisks outside the whiskers are outliers. P-values are from the Mann-Whitney nonparametric test. ICU: intensive care unit.

**Table 1.** Demographic and Clinical Characteristics of the Study Patients Based on Initial ICU Stay
	Patients with complicated course (n = 18)	Patients with uncomplicated course (n = 81)	P-value^a
^aP-values by t-test or Mann-Whitney test for continuous variables; Fisher’s exact test for categorical variables. ^bBased on n = 16 in complicated group and n = 71 in uncomplicated group. ^cBased on n = 12 in complicated group and n = 51 in uncomplicated group. *Statistical significance with a P-value less than 0.05. AKI: acute kidney injury; APACHE: Acute Physiology and Chronic Health Evaluation; BMI: body mass index; CRP: C-reactive protein; ED: emergency department; ICU: intensive care unit; IQR: interquartile range; LDH: lactate dehydrogenase; PF: PaO₂/FiO₂; RRT: renal replacement therapy; SD: standard deviation; WMC: Westchester Medical Center.
Demographics
Age, years, mean ± SD	70 (11)	56 (15)	< 0.001*
Sex, female, n (%)	9 (50%)	56 (69%)	0.13
Sex, male, n (%)	9 (50%)	25 (31%)
Smoking, n (%)			0.85
Yes	4 (22)	13 (16)
No	12 (67)	56 (69)
Unknown	2 (11)	12 (14)
Comorbidities, n (%)
Obesity (BMI ≥ 30)	8 (44%)	35 (44%)	0.99
Chronic kidney disease	2 (11%)	10 (12%)	> 0.99
Chronic pulmonary disease	2(11%)	8 (10%)	> 0.99
Coronary artery disease	3 (22%)	9 (11%)	0.25
Congestive Heart Failure	3 (17%)	7 (9%)	0.38
Stroke	0 (0%)	1 (1%)	> 0.99
Diabetes mellitus	7 (39%)	27 (33%)	0.78
Hypertension	8 (44%)	33 (41%)	0.78
Cirrhosis	1 (6%)	5 (6%)	> 0.99
Active malignancy	0 (0%)	1 (1.2%)	> 0.99
History of malignancy	3 (17%)	3 (4%)	0.11
Solid organ transplant	1 (6%)	6 (7%)	> 0.99
Charlson Comorbidity Index, mean ± SD	4.5 (3)	2.5 (2)	0.003*
Admission source, n (%)
WMC ED	6 (33%)	43 (53%)	0.13
Ward/outside transfer	12 (67%)	38 (47%)
APACHE IV score, median (IQR)^b	87 (51 - 112)	57 (43 - 72)	0.01*
Mechanical ventilation, n (%)	12 (67%)	51 (63%)	0.77
PF Ratio on intubation, median (IQR)^c	134 (65 - 257)	111 (61 - 220)	0.57
AKI, n (%)	10 (56%)	40 (49%)	0.64
New RRT, n (%)	1 (6%)	13 (16%)	0.45
Initial WMC ICU stay, days, median (IQR)	6.5 (2 - 10)	8 (3 - 22)	0.082
Treatment, n (%)
Azithromycin	16 (89%)	62 (77%)	0.35
Hydroxychloroquine	16 (89%)	66 (82%)	0.73
Corticosteroids	14 (78%)	59 (73%)	0.77
Convalescent plasma	2 (11%)	40 (49%)	0.003*
Therapeutic anticoagulation	6 (33%)	60 (74%)	0.002*
Biomarkers at ICU entry, median (IQR)
D-dimer (mg/L)	2.1 (1.3 - 19)	2.3 (0.92 - 4.2)	0.27
LDH (U/L)	515 (370 - 643)	530 (374 - 721)	0.73
CRP (mg/dL)	14.5 (9.2 - 25)	15 (7.2 - 21)	0.54
Ferritin (µg/L)	963 (412 - 1,759)	1192 (525 - 2,920)	0.50

Table 1. Demographic and Clinical Characteristics of the Study Patients Based on Initial ICU Stay

Patients with complicated course (n = 18)

Patients with uncomplicated course (n = 81)

P-value^a

^aP-values by t-test or Mann-Whitney test for continuous variables; Fisher’s exact test for categorical variables. ^bBased on n = 16 in complicated group and n = 71 in uncomplicated group. ^cBased on n = 12 in complicated group and n = 51 in uncomplicated group. *Statistical significance with a P-value less than 0.05. AKI: acute kidney injury; APACHE: Acute Physiology and Chronic Health Evaluation; BMI: body mass index; CRP: C-reactive protein; ED: emergency department; ICU: intensive care unit; IQR: interquartile range; LDH: lactate dehydrogenase; PF: PaO₂/FiO₂; RRT: renal replacement therapy; SD: standard deviation; WMC: Westchester Medical Center.

Demographics

Age, years, mean ± SD

70 (11)

56 (15)

< 0.001*

Sex, female, n (%)

9 (50%)

56 (69%)

0.13

Sex, male, n (%)

9 (50%)

25 (31%)

Smoking, n (%)

0.85

Yes

4 (22)

13 (16)

12 (67)

56 (69)

Unknown

2 (11)

12 (14)

Comorbidities, n (%)

Obesity (BMI ≥ 30)

8 (44%)

35 (44%)

0.99

Chronic kidney disease

2 (11%)

10 (12%)

> 0.99

Chronic pulmonary disease

2(11%)

8 (10%)

> 0.99

Coronary artery disease

3 (22%)

9 (11%)

0.25

Congestive Heart Failure

3 (17%)

7 (9%)

0.38

Stroke

0 (0%)

1 (1%)

> 0.99

Diabetes mellitus

7 (39%)

27 (33%)

0.78

Hypertension

8 (44%)

33 (41%)

0.78

Cirrhosis

1 (6%)

5 (6%)

> 0.99

Active malignancy

0 (0%)

1 (1.2%)

> 0.99

History of malignancy

3 (17%)

3 (4%)

0.11

Solid organ transplant

1 (6%)

6 (7%)

> 0.99

Charlson Comorbidity Index, mean ± SD

4.5 (3)

2.5 (2)

0.003*

Admission source, n (%)

WMC ED

6 (33%)

43 (53%)

0.13

Ward/outside transfer

12 (67%)

38 (47%)

APACHE IV score, median (IQR)^b

87 (51 - 112)

57 (43 - 72)

0.01*

Mechanical ventilation, n (%)

12 (67%)

51 (63%)

0.77

PF Ratio on intubation, median (IQR)^c

134 (65 - 257)

111 (61 - 220)

0.57

AKI, n (%)

10 (56%)

40 (49%)

0.64

New RRT, n (%)

1 (6%)

13 (16%)

0.45

Initial WMC ICU stay, days, median (IQR)

6.5 (2 - 10)

8 (3 - 22)

0.082

Treatment, n (%)

Azithromycin

16 (89%)

62 (77%)

0.35

Hydroxychloroquine

16 (89%)

66 (82%)

0.73

Corticosteroids

14 (78%)

59 (73%)

0.77

Convalescent plasma

2 (11%)

40 (49%)

0.003*

Therapeutic anticoagulation

6 (33%)

60 (74%)

0.002*

Biomarkers at ICU entry, median (IQR)

D-dimer (mg/L)

2.1 (1.3 - 19)

2.3 (0.92 - 4.2)

0.27

LDH (U/L)

515 (370 - 643)

530 (374 - 721)

0.73

CRP (mg/dL)

14.5 (9.2 - 25)

15 (7.2 - 21)

0.54

Ferritin (µg/L)

963 (412 - 1,759)

1192 (525 - 2,920)

0.50

**Table 2.** Patient and ICU Factors Associated With a Complicated Post-ICU Course Based on Univariate and Multivariable Logistic Regression
Variable	Crude OR (95% CI)	P-value	Adjusted OR (95% CI)	P-value
^aValues missing for 12/99 patients. ^bResult from day of ICU entry. ^cResult from day of ICU exit. ^dValues missing for 26/99 patients. ^eValues missing for 24/99 patients. APACHE: Acute Physiology and Chronic Health Evaluation; CCI: Charlson Comorbidity Index; CRP: C-reactive protein; ICU: intensive care unit; OR: odds ratio; CI: confidence interval.
CCI	1.39 (1.12 - 1.72)	0.003	1.94 (1.22 - 3.09)	0.005
APACHE IV^{a, b}	1.27 (1.05 - 1.53)	0.013	1.39 (1.05 - 1.82)	0.020
D-dimer^{c, d}	1.11 (1.03 - 1.19)	0.008	1.10 (1.00 - 1.22)	0.057
CRP^{c, e}	1.07 (1.00 - 1.13)	0.043	1.16 (1.04 - 1.30)	0.009
Anticoagulation receipt	0.18 (0.06 - 0.53)	0.002	0.07 (0.01 - 0.50)	0.008
Convalescent plasma receipt	0.13 (0.03 - 0.59)	0.009	0.09 (0.01 - 0.62)	0.015

Table 2. Patient and ICU Factors Associated With a Complicated Post-ICU Course Based on Univariate and Multivariable Logistic Regression

Variable

Crude OR (95% CI)

P-value

Adjusted OR (95% CI)

P-value

^aValues missing for 12/99 patients. ^bResult from day of ICU entry. ^cResult from day of ICU exit. ^dValues missing for 26/99 patients. ^eValues missing for 24/99 patients. APACHE: Acute Physiology and Chronic Health Evaluation; CCI: Charlson Comorbidity Index; CRP: C-reactive protein; ICU: intensive care unit; OR: odds ratio; CI: confidence interval.

CCI

1.39 (1.12 - 1.72)

0.003

1.94 (1.22 - 3.09)

0.005

APACHE IV^{a, b}

1.27 (1.05 - 1.53)

0.013

1.39 (1.05 - 1.82)

0.020

D-dimer^{c, d}

1.11 (1.03 - 1.19)

0.008

1.10 (1.00 - 1.22)

0.057

CRP^{c, e}

1.07 (1.00 - 1.13)

0.043

1.16 (1.04 - 1.30)

0.009

Anticoagulation receipt

0.18 (0.06 - 0.53)

0.002

0.07 (0.01 - 0.50)

0.008

Convalescent plasma receipt

0.13 (0.03 - 0.59)

0.009

0.09 (0.01 - 0.62)

0.015

**Table 3.** Descriptive Summary of Notable Ward Stay Characteristics of the Patients With a Complicated Post-ICU Course
Patient	Days on ward	Death on ward	Return to ICU	IMV upon return	Final disposition	Notable ward events
^aWard deaths after initial ICU downgrade. ^bPatient died on the ward after repeat ICU downgrade. AMS: altered mental status; DNI: do not reintubate; DNR: do not resuscitate; ICU: intensive care unit; IMV: invasive mechanical ventilation; NA: not applicable; PEA: pulseless electrical activity; SVT: superventricular tachycardia.
1^a	2	Y	NA	NA	NA	Died as DNR/DNI
2^a	7	Y	NA	NA	NA	New atrial flutter; new elevated troponin; QTc = 500 ms; bacteremia
3^a	6	Y	NA	NA	NA	Persistent AMS; new bradycardia
4^a	2	Y	NA	NA	NA	New atrial fibrillation; new bradycardia; QTc > 600 ms
1	1	N	Y	Y	ICU death	New elevated troponin
2	5	N	Y	Y	Facility discharge	Persistent AMS
3	3	N	Y	Y	Facility discharge	Persistent AMS; respiratory distress after swallow evaluation
4	1	N	Y	Y	ICU death	New atrial fibrillation; new elevated troponin; QTc = 500 ms; new fever with leukocytosis
5	3	N	Y	Y	Facility discharge	New episodes of SVT
6	2	N	Y	Y	Facility discharge	New episode of SVT; new elevated troponin; QTc > 500 ms
7	12	N	Y	N	Facility discharge	Fever and worsening infiltrates
8	1	N	Y	Y	Ward death^b	Empyema; PEA arrest
9	1	N	Y	Y	ICU death	None identified
10	2	N	Y	Y	Facility discharge	None identified
11	1	N	Y	Y	ICU death	None identified
12	16	N	Y	Y	ICU death	Bacteremia
13	8	N	Y	Y	Facility discharge	Persistent AMS; new sinus pauses > 30 s
14	11	N	Y	Y	Facility discharge	New elevated troponin
ICU return, N = 14 (78%)	2.5 (1 - 8.75)	None	All	13 (93%)	Hospital mortality 6 (43%)
Total, N = 18	2.5 (1.25 - 6.76)	4 (22%)	14 (78%)	13 (72%)	Hospital mortality: 10 (56%)

Table 3. Descriptive Summary of Notable Ward Stay Characteristics of the Patients With a Complicated Post-ICU Course

Patient

Days on ward

Death on ward

Return to ICU

IMV upon return

Final disposition

Notable ward events

^aWard deaths after initial ICU downgrade. ^bPatient died on the ward after repeat ICU downgrade. AMS: altered mental status; DNI: do not reintubate; DNR: do not resuscitate; ICU: intensive care unit; IMV: invasive mechanical ventilation; NA: not applicable; PEA: pulseless electrical activity; SVT: superventricular tachycardia.

1^a

Died as DNR/DNI

2^a

New atrial flutter; new elevated troponin; QTc = 500 ms; bacteremia

3^a

Persistent AMS; new bradycardia

4^a

New atrial fibrillation; new bradycardia; QTc > 600 ms

ICU death

New elevated troponin

Facility discharge

Persistent AMS

Facility discharge

Persistent AMS; respiratory distress after swallow evaluation

ICU death

New atrial fibrillation; new elevated troponin; QTc = 500 ms; new fever with leukocytosis

Facility discharge

New episodes of SVT

Facility discharge

New episode of SVT; new elevated troponin; QTc > 500 ms

Facility discharge

Fever and worsening infiltrates

Ward death^b

Empyema; PEA arrest

ICU death

None identified

Facility discharge

None identified

ICU death

None identified

ICU death

Bacteremia

Facility discharge

Persistent AMS; new sinus pauses > 30 s

Facility discharge

New elevated troponin

ICU return, N = 14 (78%)

2.5 (1 - 8.75)

None

All

13 (93%)

Hospital mortality 6 (43%)

Total, N = 18

2.5 (1.25 - 6.76)

4 (22%)

14 (78%)

13 (72%)

Hospital mortality: 10 (56%)