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Since the start of the COVID-19 pandemic, there have been over 2 million deaths globally. Acute respiratory distress syndrome (ARDS) may be the main cause of death.
This study aimed to describe the clinical features, outcomes, and ARDS characteristics of patients with COVID-19 admitted to the intensive care unit (ICU) in Chongqing, China.
The epidemiology of COVID-19 from January 21, 2020, to March 15, 2020, in Chongqing, China, was analyzed retrospectively, and 75 ICU patients from two hospitals were included in this study. On day 1, 56 patients with ARDS were selected for subgroup analysis, and a modified Poisson regression was performed to identify predictors for the early improvement of ARDS (eiARDS).
Chongqing reported a 5.3% case fatality rate for the 75 ICU patients. The median age of these patients was 57 (IQR 25-75) years, and no bias was present in the sex ratio. A total of 93% (n=70) of patients developed ARDS during ICU stay, and more than half had moderate ARDS. However, most patients (n=41, 55%) underwent high-flow nasal cannula oxygen therapy, but not mechanical ventilation. Nearly one-third of patients with ARDS improved (arterial blood oxygen partial pressure/oxygen concentration >300 mm Hg) in 1 week, which was defined as eiARDS. Patients with eiARDS had a higher survival rate and a shorter length of ICU stay than those without eiARDS. Age (<55 years) was the only variable independently associated with eiARDS, with a risk ratio of 2.67 (95% CI 1.17-6.08).
A new subphenotype of ARDS—eiARDS—in patients with COVID-19 was identified. As clinical outcomes differ, the stratified management of patients based on eiARDS or age is highly recommended.
In December 2019, Wuhan, Hubei Province, China, reported a cluster of pneumonia cases of unknown cause, later identified as COVID-19 [
The leading cause of COVID-19–related death may be severe respiratory failure caused by acute respiratory distress syndrome (ARDS) [
This study aimed to describe the epidemiology, clinical features, laboratory findings, treatments, and outcomes of intensive care unit (ICU) patients with COVID-19 in Chongqing, China, which neighbors Hubei Province. In addition, a subphenotype of ARDS—early improvement of ARDS (eiARDS)—which occurred in about one-third of patients, was identified. eiARDS predicted a favorable clinical outcome.
This retrospective cohort study included two cohorts of ICU patients from the Chongqing Public Health Medical Center and the Chongqing Three Gorges Central Hospital (Chongqing, China), both of which were designated hospitals for the treatment of patients with COVID-19 in Chongqing. Patients admitted to the ICU between January 21, 2020 (the date the first patient was admitted), and March 15, 2020 (the date the last patient was discharged during the first wave), were enrolled in this study.
Patients with COVID-19 were confirmed by a positive real-time reverse transcription–polymerase chain reaction (RT-PCR) assay using nasal swab specimens per WHO guidance [
The two designated hospitals were Grade A hospitals in China, and all case data were retrieved from their electronic case system. Epidemiological and demographic data, symptoms, underlying diseases, comorbidities, treatments, clinical course, and outcome data of the patients were recorded in a spreadsheet. Vital signs, arterial blood gas analysis, laboratory data, acute physiology and chronic health evaluation II, and the sequential organ failure assessment score were recorded on specified dates (day 0: admission to hospital; day 1: admission to ICU; day 3, day 7, and day 14) for each patient. If any question emerged regarding the case data, clarification was sought from the treating team physician. As data collection was completed, another doctor was responsible for checking and integrating the data. The proportion of pneumonia volume was calculated by the Pulmonary Infection–Assisted Diagnosis System (V1.7.1) based on computed tomography (CT) imaging.
ARDS was diagnosed according to the Berlin definition [
SPSS 26.0 (IBM Corp) was used for statistical analysis. Normally distributed continuous variables were presented as mean (SD), and the independent Student
The study was approved by the Research Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University, the Chongqing Public Health Medical Center, and the Chongqing Three Gorges Central Hospital. Written informed consent was waived by the ethics committees of the designated hospitals for emerging infectious diseases.
Original data can be requested from the corresponding author.
From January 21 to March 15, 2020, Chongqing reported 576 new cases of COVID-19 and 6 deaths. In this study, 75 ICU patients from two hospitals were recruited, including 48 severe patients, 27 critically ill patients, and 4 deceased patients.
A comparison of clinical characteristics between the two groups is shown in
ARDS developed in most patients (n=70, 93%), and more than half (n=38, 51%) had moderate ARDS (
Clinical characteristics of severe or critically ill patients with COVID-19 admitted to the intensive care unit in Chongqing, China (from January 21 to March 15, 2020).
Characteristic | Total (N=75) | Severe (n=48) | Critically ill (n=27)a | |||
Age (years), median (IQR) | 57 (25-75) | 56 (47-70) | 63 (51-69) | .57 | ||
|
.64 | |||||
Female | 36 (48) | 24 (50) | 12 (44) | |||
Male | 39 (52) | 24 (50) | 15 (56) | |||
Smoking | 9 (12) | 1 (2) | 8 (30) | .002 | ||
|
.052 | |||||
Recent travel to Hubei Province | 16 (21) | 13 (27) | 3 (11) | |||
Contact with patients from Hubei Province | 24 (32) | 18 (38) | 6 (22) | |||
Contact with confirmed patients | 17 (23) | 7 (15) | 10 (37) | |||
No definite epidemiological link | 18 (24) | 10 (21) | 8 (30) | |||
|
||||||
Hypertension | 14 (19) | 8 (17) | 6 (22) | .55 | ||
Diabetes | 20 (27) | 12 (25) | 8 (30) | .66 | ||
Chronic cardiac disease | 7 (9) | 6 (13) | 1 (4) | .40 | ||
Chronic obstructive pulmonary disease | 4 (5) | 4 (8) | 0 (0) | .31 | ||
Malignancy | 1 (1) | 1 (2) | 0 (0) | >.99 | ||
|
||||||
Fever | 51 (68) | 28 (58) | 23 (85) | .02 | ||
Cough | 62 (83) | 40 (83) | 22 (81) | >.99 | ||
Expectoration | 29 (39) | 21 (44) | 8 (30) | .23 | ||
Dyspnea | 43 (57) | 23 (48) | 20 (74) | .03 | ||
Myalgia | 20 (27) | 12 (25) | 8 (30) | .66 | ||
Headache | 9 (12) | 7 (15) | 2 (7) | .58 | ||
Diarrhea | 7 (9) | 4 (8) | 3 (11) | >.99 | ||
|
||||||
|
70 (93) | 43 (90) | 27 (100) | .01 | ||
None | 5 (7) | 5 (10) | 0 (0) | |||
Mild | 10 (13) | 9 (19) | 1 (4) | |||
Moderate | 38 (51) | 25 (52) | 13 (48) | |||
Severe | 22 (29) | 9 (19) | 13 (48) | |||
Pneumothorax | 1 (1) | 0 (0) | 1 (4) | .77 | ||
Bacterial pneumoniac | 4 (5) | 3 (6) | 1 (4) | >.99 | ||
Cardiac injury | 14 (19) | 7 (15) | 7 (26) | .23 | ||
Liver injury | 19 (25) | 10 (21) | 9 (33) | .23 | ||
Kidney injury | 8 (11) | 5 (10) | 3 (11) | >.99 | ||
Shock | 7 (9) | 0 (0) | 7 (26) | .001 | ||
Leukopenia | 19 (25) | 11 (23) | 8 (30) | .52 | ||
Lymphopenia | 71 (95) | 46 (96) | 25 (93) | .95 | ||
Thrombocytopenia | 20 (27) | 9 (19) | 11 (41) | .04 | ||
|
||||||
High-flow nasal cannula | 41 (55) | 20 (42) | 21 (78) | .003 | ||
|
||||||
Noninvasive | 26 (35) | 0 (0) | 26 (96) | <.001 | ||
Invasive | 7 (9) | 0 (0) | 7 (26) | .001 | ||
Prone position ventilation | 7 (9) | 0 (0) | 7 (26) | .001 | ||
Extracorporeal membrane oxygenation | 3 (4) | 0 (0) | 3 (11) | .08 | ||
Renal replacement therapy | 3 (4) | 0 (0) | 3 (11) | .08 | ||
Vasoconstrictive agents | 7 (9) | 0 (0) | 7 (26) | .001 | ||
Antiviral agents | 75 (100) | 48 (100) | 27 (100) | —d | ||
Antibacterial agents | 62 (83) | 37 (77) | 25 (93) | .17 | ||
Antifungal | 12 (16) | 4 (8) | 8 (30) | .04 | ||
Glucocorticoids | 46 (61) | 22 (46) | 24 (89) | <.001 | ||
Immunoglobulin | 30 (40) | 13 (27) | 17 (63) | .002 | ||
Thymopeptides | 63 (84) | 37 (77) | 26 (96) | .06 | ||
Traditional Chinese medicine | 65 (87) | 41 (85) | 24 (89) | .94 |
aFour patients who died in the ICU were included.
bARDS stages were defined by the worst PaO2/FiO2 value.
cBacterial pneumonia was confirmed by sputum or alveolar lavage fluid culture.
dNot applicable.
The clinical course and outcomes of patients with COVID-19 in Chongqing are shown in
Clinical course and outcomes of patients with COVID-19 admitted to the intensive care unit (ICU) in Chongqing, China (from January 21 to March 15, 2020).
Clinical course and outcomes | Value | |
|
||
Diagnosis confirmed by PCRb test | 5 (2-7) | |
Hospital admission | 7 (4-8) | |
Acute respiratory distress syndrome | 7 (6-10) | |
ICU admission | 8 (6-11) | |
Ventilation | 10 (7-14) | |
Cessation of viral sheddingc | 20 (16-26) | |
Deathd | 16 (15-28) | |
Length of ICU stay | 13 (9-19) | |
Length of hospital stay | 22 (16-34) | |
28-day mortalityd | 4 (5.3) | |
28-day mechanical ventilation dependency | 1 (1.3) | |
|
||
ICU | 4 (66.7) | |
Emergency department | 2 (33.3) |
aTwo patients without any symptoms until hospital admission were excluded from statistical analysis.
bPCR: polymerase chain reaction.
cTwo consecutive negative nasal swab PCR tests performed at an interval of least 24 hours).
dFour patients who died in the ICU were included.
In order to clarify the characteristics of ARDS in patients with COVID-19, 56 patients with ARDS (PaO2/FiO2 <300 mm Hg) on day 1 (first day of ICU admission) were included for a subgroup analysis. These patients were then divided into two groups based on the severity of illness on day 7: eiARDS patients with PaO2/FiO2 ≥300 mm Hg and non-eiARDS patients with PaO2/FiO2 <300 mm Hg (
Of the 56 patients with ARDS, a total of 18 patients had eiARDS. No significant differences were found in PaO2/FiO2 on day 1 (
A Poisson regression analysis was performed to determine the factors associated with eiARDS.
Comparison of patients with and without early improvement of acute respiratory distress syndrome (eiARDS). (A) All patients with ARDS on day 1, divided into two groups (eiARDS and non-eiARDS) according to PaO2/FiO2 on day 7. (B) No significant difference between the two groups in the PaO2/FiO2 on day 1. (C) No significant difference between the two groups in the proportion of pneumonia volume on day 1. (D) The length of intensive care unit stay exhibited differences between the two groups.
Univariate and multivariate analysis of predictors for the early improvement of acute respiratory distress syndrome (eiARDS) in patients with COVID-19 in Chongqing, China (from January 21 to March 15, 2020).
Characteristic | eiARDS (n=18) | Non-eiARDS (n=38) | Relative risk (95% CI) | |||
|
||||||
|
||||||
≥55 | 6 (33.3) | 26 (68.4) | 1 (reference) | —b | ||
<55 (univariate) | 12 (66.7) | 12 (31.6) | 2.67 (1.17-6.08) | .02 | ||
<55 (multivariate) | — | — | 2.36 (1.05-5.23) | .04 | ||
Male sex (vs female), n (%) | 12 (66.7) | 19 (50.0) | 1.61 (0.71-3.70) | .26 | ||
Time of symptom onset to intensive care unit admission, median (days) | 7.5 | 8 | 1.02 (0.92-1.14) | .69 | ||
Smoking, n (%) | 4 (22.2) | 4 (10.5) | 1.71 (0.75-3.90) | .20 | ||
Hypertension, n (%) | 2 (11.2) | 7 (18.4) | 0.65 (0.18-2.36) | .52 | ||
Diabetes, n (%) | 4 (22.2) | 9 (26.3) | 0.86 (0.34-2.18) | .75 | ||
Chronic obstructive pulmonary disease, n (%) | 1 (5.6) | 3 (7.9) | 0.77 (0.13-4.36) | .76 | ||
APACHE IIc, median | 6.5 | 9 | 0.90 (0.76-1.05) | .17 | ||
SOFAd, median | 4 | 3 | 0.97 (0.67-1.42) | .89 | ||
|
||||||
<37.3 °C | 15 (83.3) | 18 (47.4) | 1 (reference) | — | ||
≥37.3 °C (univariate) | 3 (16.7) | 20 (52.6) | 0.33 (0.11-1.02) | .054 | ||
|
||||||
<100 | 13 (72.2) | 33 (86.8) | 1 (reference) | — | ||
≥100 | 5 (27.8) | 5 (13.2) | 1.77 (0.82-3.83) | .15 | ||
|
||||||
<30 | 15 (83.3) | 37 (97.4) | 1 (reference) | — | ||
≥30 | 3 (16.7) | 1 (2.6) | 1.17 (0.48-2.86) | .73 | ||
|
||||||
<140 mm Hg | 16 (88.9) | 35 (92.1) | 1 (reference) | — | ||
≥140 mm Hg | 2 (11.1) | 3 (7.9) | 1.28 (0.41-4.02) | .68 | ||
Ventilation (vs non) | 2 (11.1) | 5 (13.2) | 0.88 (0.25-3.02) | .83 | ||
Proportion of pneumonia volume, median | 17.6 | 20.3 | 0.98 (0.94-1.02) | .28 | ||
|
||||||
|
||||||
7.35-7.45 | 4 (22.2) | 12 (31.6) | 1 (reference) | — | ||
>7.45 | 14 (77.8) | 26 (65.8) | 1.44 (0.56-3.70) | .45 | ||
|
||||||
34-45 mm Hg | 9 (50.0) | 21 (55.3) | 1 (reference) | — | ||
≤34 mm Hg | 8 (44.4) | 17 (44.7) | 1.07 (0.48-2.35) | .87 | ||
|
||||||
≥60 mm Hg | 14 (77.8) | 23 (60.5) | 1 (reference) | — | ||
<60 mm Hg | 4 (22.2) | 15 (39.5) | 0.56 (0.21-1.46) | .23 | ||
|
||||||
<4 (univariate) | 7 (38.9) | 6 (16.2) | 2.21 (1.04-4.73) | .04 | ||
<4 (multivariate) | — | — | 1.94 (0.97-3.86) | .06 | ||
4-10 | 9 (50.0) | 28 (75.7) | 1 (reference) | — | ||
>10 (univariate) | 2 (11.1) | 3 (8.1) | 1.64 (0.49-5.54) | .42 | ||
>10 (multivariate) | — | — | 1.37 (0.48-3.89) | .55 | ||
|
0.8 | 0.8 | 2.18 (0.79-6.02) | .13 | ||
|
||||||
≥100 | 16 (88.9) | 35 (94.6) | 1 (reference) | — | ||
<100 | 2 (11.1) | 2 (5.4) | 1.59 (0.55-4.60) | .39 | ||
|
||||||
3.5-4.5 mmol/L | 14 (77.8) | 25 (67.6) | 1 (reference) | — | ||
<3.5 mmol/L | 3 (16.7) | 11 (29.7) | 0.61 (0.21-1.82) | .38 | ||
|
||||||
135-145 mmol/L | 10 (55.6) | 20 (54.1) | 1 (reference) | — | ||
<135 mmol/L | 8 (44.4) | 16 (43.2) | 1.00 (0.47-2.14) | >.99 | ||
|
||||||
≥40 g/L | 3 (17.6) | 4 (10.8) | 1 (reference) | — | ||
<40 g/L | 14 (82.4) | 33 (89.2) | 0.70 (0.27-1.82) | .46 | ||
|
||||||
≤17.1 μmol/L | 10 (55.6) | 27 (71.1) | 1 (reference) | — | ||
>17.1 μmol/L | 8 (44.4) | 11 (28.9) | 1.56 (0.74-3.29) | .25 | ||
|
||||||
≤40 U/L | 13 (72.2) | 23 (60.5) | 1 (reference) | — | ||
>40 U/L | 5 (27.8) | 15 (39.5) | 0.69 (0.29-1.66) | .41 | ||
|
||||||
≤200 U/L | 13 (81.2) | 28 (75.7) | 1 (reference) | — | ||
>200 U/L | 3 (18.8) | 9 (24.3) | 0.67 (0.27-2.32) | .79 | ||
|
||||||
≤0.014 ng/mL | 9 (90.0) | 19 (86.4) | 1 (reference) | — | ||
>0.014 ng/mL | 1 (10.0) | 3 (13.6) | 0.78 (0.13-4.62) | .78 | ||
|
||||||
≤0.55 μg/L | 9 (81.8) | 15 (39.5) | 1 (reference) | — | ||
>0.55 μg/L | 2 (18.2) | 23 (60.5) | 0.96 (0.40-2.33) | .93 | ||
|
||||||
≤0.046 ng/ml | 8 (53.3) | 6 (16.7) | 1 (reference) | — | ||
>0.046 ng/ml | 7 (46.7) | 30 (83.3) | 0.49 (0.23-1.05) | .07 | ||
High-sensitivity C reaction protein (mg/L), median | 44.6 | 95.2 | 0.99 (0.98-1.00) | .07 |
aTwo variables (age, white blood cell count) were chosen for multivariable analysis.
bNot applicable.
cAPACHE: acute physiology and chronic health evaluation.
dSOFA: sequential organ failure assessment.
ePaCO2: arterial partial pressure of carbon dioxide.
fPaO2: arterial partial pressure of oxygen.
In this study, the mortality rate associated with COVID-19 in Chongqing was 1.04%, and the 28-day case fatality rate of ICU patients was 5.3%. ARDS developed in 93% of ICU patients, and HFNC was the most commonly used type of oxygen therapy. About one-third of patients with ARDS improved in 1 week, which we defined as eiARDS. Patients younger than 55 years were more likely to exhibit eiARDS.
The mortality of COVID-19 varied widely across different periods and areas. In the early stage of the outbreak, Wuhan reported a mortality rate of 4.3% among hospitalized patients [
ARDS is the primary factor that increases mortality. According to the Berlin definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%, 32%, and 45%, respectively) [
In our study, nearly one-third of patients with ARDS recovered in 1 week, which we defined as eiARDS. However, eiARDS was found in only 18% of patients with mild ARDS caused by other factors, with 36% of patients persisting and 46% worsening during the first week after ARDS onset [
Regardless of the reasons why the proportion of eiARDS was high, paying attention to eiARDS itself is clinically meaningful. Early or rapid improvements in ARDS has always been associated with increased survival or better outcomes [
This study had several limitations. First, because of the retrospective study design, laboratory tests (except arterial blood gas analysis, which was performed daily) might not be performed for all patients at a specific time; the missing data were replaced by values obtained within the prior 2 days. Second, although the treatment strategies of the two hospitals were in accordance with the guidelines issued by the Chinese National Health Commission, some of the treatments were different, such as the composition of traditional Chinese medicine, leading to different clinical outcomes. Third, the sample size was relatively small, and some of the conclusions need to be verified using multiple care centers and larger sample sizes.
A new subphenotype of ARDS—eiARDS—in patients with COVID-19 was identified. As clinical outcomes differ, the stratified management of patients based on eiARDS or age is highly recommended.
acute respiratory distress syndrome
computed tomography
early improvement of ARDS
oxygen concentration
high-flow nasal cannula
intensive care unit
arterial blood oxygen partial pressure
polymerase chain reaction
real-time reverse transcription–polymerase chain reaction
upper limit of normal
World Health Organization
The authors thank the patients described in this study, the health care personnel who cared for them, the staff members of the Health Commission of Chongqing City, and the staff members of the Chongqing Center for Disease Control and Prevention. We thank Dr Weijun Zheng (Zhejiang Chinese Medical University, China) for his professional statistical advice.
This work was supported by Chongqing Special Research Project for Novel Coronavirus Pneumonia Prevention and Control (#cstc2020jscx-fyzxX0012) and Emergency Research Project of COVID-19 of the Chongqing Health Commission (#2020NCPZX04).
ZZ was responsible for conceptualization, methodology, formal analysis, and writing of the original draft. XY contributed to methodology, formal analysis, and writing of the original draft. HD was involved in the investigation and project administration. CZ and XR contributed to the investigation. YS was responsible for the investigation and resources. AZ was responsible for conceptualization, resources, supervision, and review and editing of the manuscript. MY contributed to resources and supervision. This manuscript was approved by all authors for publication.
None declared.