Characteristics and clinical outcomes of patients with COVID-19-related ARDS
From 26 January to 1 April 2020, 338 patients with COVID-19 confirmed by laboratory findings or otherwise clinical diagnosis were treated at the two hospitals in Hubei province of China. Of these, 70 patients developed ARDS. We included 65 of these cases with laboratory confirmation and excluded five cases. The details of enrolment are provided in Fig. 1.
The median age of the 65 included ARDS patients was 67.0 years (IQR, 56.0–78.0), with the 53.8% over 65 years and the 70.8% males (Table 1). The median body mass index (BMI) was 24.4 kg/m2 (IQR, 22.4–26.7). More than two-thirds of patients (n = 44) had at least three symptoms. The most three self-reported symptoms were fever (84.6%), cough (70.8%), and shortness of breath (43.1%). Vital signs evaluated at hospital admission revealed fever in 23 patients (35.4%) and median 20.0 breaths per minute (IQR, 20.0–25.0). Forty-four patients had at least one comorbidity. More than two-thirds of the patients (n = 45) were graded as severe pneumonia by physicians. From the symptom onset to hospital admission the median number of days was 8.0 (IQR, 5.0–10.0), from hospital admission to ARDS diagnosis it was only 1.0 (IQR, 0.0–4.0), from symptom onset to ARDS diagnosis it was 11.0 (IQR, 8.0–13.0). All patients demonstrated bilateral pulmonary infiltrates. The median oxygenation index (OI) at ARDS diagnosis was 184.5 (IQR, 134.0–230.0) and 47.7% of all patients had moderate ARDS at the beginning (OI between 199 and 100) (Table 1). Most patients received antiviral and empiric antibiotic therapies. The 78.5% of the patients took methylprednisolone (glucocorticoid) and 24.6% took vasopressors. Nearly half required ICU-level care, eight adopted prone position ventilation, and six and four received CRRT and ECMO respectively, to sustain life. The median ICU and hospital stays were 15.0 days (IQR, 10.0–20.0) and 21.0 days (IQR, 12.0–34.0). Twenty-four deaths (38.1%) occurred, and the main cause was acute respiratory condition (62.5%). For mild, moderate, and severe ARDS, the mortality rates were 20.0%, 41.9% and 85.7% respectively.
Laboratory indices tested at admission (Table 2) suggested that most patients had systemic hyperinflammation, indicated by the increased erythrocyte sedimentation rate (ESR), C-reactive protein level and procalcitonin level. Quite a few patients demonstrated reduced albumin/globulin ratio and increased total bilirubin and aspartate transaminase levels, suggesting liver injury, and elevated lactate dehydrogenase and cardiac troponin I levels, indicating heart injury. Approximately four-fifths of the patients had lymphocytopenia. Some patients were suspected of having pancreatic injury indicated by the high blood glucose level, and kidney injury based on the elevated serum creatinine level and reduced glomerular filtration rate (GFR). Next, a high international normalized ratio, prolonged prothrombin time and elevated D-dimer level were reported in several patients. Some patients demonstrated leukocytosis, neutrophilia, thrombocytopenia and reduced hemoglobin concentrations.
Comparisons among patients with non-invasive respiratory supports, early, and late intubation
Compared with the late-intubation group, patients with early intubation had significantly shorter time from symptom onset to intubation (P = 0.023), from hospital admission to intubation (P = 0.011), and from ARDS diagnosis to intubation (P < 0.001) (Fig. 2A). We observed the differences on OI values (P = 0.015) at ARDS diagnosis and proportions of ARDS classifications (P = 0.052) among no-intubation, early-intubation, and late-intubation groups. Patients with early intubation presented the lowest OI ratios (median, 133.9; IQR 98.3-183.2) and the highest proportion of moderate and severe ARDS (90%). But patients with late intubation had a slightly higher OI ratios (median, 159.0; IQR 134.0-203.0) compared to early-intubation group. Consequently, these late intubation patients received the most aggressive therapies including glucocorticoids (100.0%), vasopressors (50.0%), CRRT (50.0%), prone position ventilation (50.0%), ECMO (50.0%), and ICU-level care (80.0%) in the context of the associated differences occurring among the three groups (P = 0.016, P = 0.007, P < 0.001, P = 0.001, P < 0.001, P < 0.001). The mortality rate at discharge in the late-intubation group was 90.0% compared with 50.0% in the early-intubation group and 23.3% in the no-intubation group (P < 0.001, Table 3, Fig. 2B). The hospital survival probability of the late-intubation group was the lowest among the three groups (Fig. 2C).
Risk factors associated with intubation and hospital death
As summarized in Table 4, patients aged equal and older than 65 years (RR, 2.56; 95% CI 1.06-6.18, P = 0.037), had fatigue (RR, 2.63; 95% CI 1.30-5.31, P = 0.007), hypertension (RR, 2.05; 95% CI 1.03-4.08, P = 0.042), GFR < 80 ml/min/1.73m2 (RR, 2.13; 95% CI 1.02-4.48, P = 0.045) at admission, lower OI ratio (higher values RR, 0.99; 95% CI 0.99- 0.99, P = 0.000), or OI ratio less than 150 (RR, 2.61; 95% CI 1.25-5.43, P = 0.010) at ARDS diagnosis were more likely to have the intubation.
Regarding hospital death, the ARDS patients on the intubation had 3.01 RR (95% CI, 1.63-5.62, P = 0.000), and the patients receiving the late intubation had 3.18 RR (95% CI, 1.98-5.12, P = 0.000). ARDS patients who were older (RR, 2.56; 95% CI 1.06-6.18, P = 0.037), aged equal and over 65 years (RR, 2.56; 95% CI 1.06-6.18, P = 0.037), had fatigue (RR, 2.56; 95% CI, 1.01–6.08, P = 0.047) were more likely to die in hospital. Patients demonstrating lower OI ratio (higher values RR, 0.99; 95% CI, 0.99–1.00, P < 0.001), OI ratios lower than 200 (RR, 2.50; 95% CI, 1.07-5.83, P = 0.034), 150 (RR, 2.43; 95% CI, 1.30-4.57, P = 0.006) or 100 (RR, 2.67; 95% CI, 1.64-4.34, P < 0.001) were associated with hospital death.