Baseline characteristics
From February 2020 to July 2021, 107 patients with severe COVID-19 pneumonia were enrolled. Of these, 1 patient were excluded analysis because of missing data. Ultimately, a total of 106 patients were evaluated in this study (Fig. 1). Table 1 shows individual baseline clinical and outcome data in the present study population. The median age was 66 years (interquartile range [IQR]: 55 to 72). Of these patients, 77 (73%) were male and 29 (27%) were female. Hemodynamics indicated by blood pressure (BP) and heart rate (HR) was preserved at hospital arrival. More than 80% of the study population was diagnosed as pneumonia. Comorbidity was shown, including interstitial pneumonia, chronic obstructive pulmonary disease, hypertension, diabetes, chronic kidney disease, heart failure, and liver cirrhosis. More than 50% (n=59/106) required MV for severe respiratory failure 0.5 hours (IQR: 0.3 to 1.4) after hospital admission (vented group), while the remaining patients did not during hospitalization (unvented group).
Comparisons of clinical and laboratory data
There were not any significant differences of age, sex, body mass index (BMI), and smoking between vented group and unvented group. With regarding to hemodynamics at hospital arrival, BP and HR did not show any significant differences between the 2 groups. However, respiratory status, as indicated by S/F ratio, was significantly worse before intubation in the vented group compared with in the unvented group. Alternatively, there were no significant differences in the prevalence of comorbidities between the two groups. Comparisons of laboratory data between the 2 groups showed significant increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), C-reactive protein (CRP), and BG and decreases in the lymphocyte counts in the vented group (Table 2).
Prediction for the impending MV use
We evaluated the associations of significant nine variables in the univariate analysis, including S/F ratio, lymphocyte count, AST, ALT, ALP, LDH, BUN, BG, and CRP with the use of MV using the area under receiver operating characteristic curve (AUROC) obtained from a 10-split crossover test. The combination of these nine variables showed an AUC of 0.89 [0.75-1.00] with a sensitivity of 0.91, specificity of 0.81, positive predictive value (PPV) of 0.90, and negative predictive value (NPV) of 0.83 (Table 3).
The beta regression coefficient selected from a multivariable logistic regression model using these variables is shown in the supplemental Fig. 1. Based on significant beta regression coefficient with > 0.5 of their values, we identified the top four variables to predict MV use, including S/F ratio, BG, lymphocyte counts, and ALT. The combination of the four variables showed higher accuracy (AUC of 0.89 [0.83-0.95]) compared to S/F ratio or BG alone (AUC of 0.84 [0.76-0.91] or AUC of 0.75 [0.66-0.91], respectively) (Fig. 2, Table 4), with a sensitivity of 1.00, specificity of 0.82, PPV of 0.85, and NPV of 1.00 (Table 4).
We further evaluated a predictive value of combing S/F ratio and BG, which can be easily and immediately measured, on the use of MV. The accuracy of this combination in the prediction (AUC: 0.88 [0.82-0.94) was nearly equal to that of the combing 4 variables, with a sensitivity of 1.00, specificity of 0.73, PPV of 0.79, and NPV of 1.00 (Table 4). A novel combination of S/F ratio and BG is likely to allow accurately and easily predict the impending MV use in not only ER but also ambulance and home.
Clinical utility of combining BG level and S/F ratio at hospital admission was tested with Kaplan-Meier event-incidence curves of MV use that were constructed according to above or below optimal cutoffs defined by AUROC analysis (BG: 138 mg/dL, S/F ratio: 300). In high-risk patients with low S/F ratio (≦ 300), MV use rate at the 3-day follow-up period did not show a significant difference between low BG (< 138 mg/dL) and high BG (≧ 138 mg/dL) (n=11/14 (79%) vs. n=34/37 (92%), respectively, P = 0.48). However, in patients with high S/F ratio (> 300), those with high BG had a significantly higher MV use rate compared to those with low BG (n=10/20 (50%) vs. n=4/35 (11%), respectively, P < 0.01) (Fig. 3). Importantly, this suggests that measuring BG level at hospital admission allows identifying patients at high risk for impending MV use from population with preserved respiratory status, which supports a better accuracy of combining BG and S/F ratio than S/F ratio alone.