Table 1.
Clinical Features of Patients With COVID-19 Pneumonia Upon Admission (Panel A) and Significant Risk Factors for ICU Admission and Mechanical Ventilation Using Binary Logistic Regression and Multinomial Logistic Regression Analyses, Respectively (Panel B).
| Panel A | ||||
|---|---|---|---|---|
| Variable | Total N = 240 |
Non-ICU N = 115 |
ICU-admitteda N = 125 |
P Valueb |
| Age, mean (SD), years | 57.7 (17.8) | 58.7 (20.4) | 56.8 (15.1) | .422 |
| Male gender, n (%) | 161 (67) | 68 (59) | 93 (74) | .012 |
| Body mass index, mean (SD), kg/m2 | 28.6 (5.0) | 27.4 (4.6) | 29.4 (5.1) | .002 |
| Pre-existing comorbid conditions, n (%)c | 143 (60) | 64 (56) | 79 (63) | .234 |
| Chronic respiratory disease | 33 (14) | 14 (12) | 19 (15) | .496 |
| Cardiac disease | 36 (15) | 17 (15) | 19 (15) | .928 |
| Hypertension | 92 (38) | 44 (38) | 48 (38) | .982 |
| Diabetes mellitus | 34 (14) | 14 (12) | 20 (16) | .427 |
| Chronic renal disease | 29 (12) | 13 (11) | 16 (13) | .722 |
| Duration of onset of symptoms to hospital admission, median (IQR), days | 7 (4; 8) | 7 (4; 8) | 7 (4; 8) | .937 |
| Laboratory values, median (IQR) | ||||
| Lymphocytes at day 1, ×109/L | 0.8 (0.6; 1.1) | 0.8 (0.6; 1.1) | 0.7 (0.5; 1.0) | .016 |
| Lymphocytes at day 3, ×109/L | 0.8 (0.6; 1.2) | 0.9 (0.7; 1.3) | 0.7 (0.5; 1.0) | .001 |
| Lymphocytes at day 5, ×109/L | 0.8 (0.5; 1.1) | 1.1 (0.7; 1.4) | 0.6 (0.5; 0.9) | <.001 |
| C-reactive protein at day 1, mg/L | 79 (34; 156) | 53 (23; 110) | 122 (67; 192) | <.001 |
| C-reactive protein at day 3, mg/L | 98 (46; 170) | 65 (32; 124) | 136 (73; 205) | <.001 |
| C-reactive protein at day 5, mg/L | 53 (26; 111) | 46 (24; 71) | 65 (28; 148) | .027 |
| C-reactive protein-to-lymphocyte ratio at day 1 | 101 (41; 244) | 72 (27; 127) | 179 (64; 351) | <.001 |
| Neutrophils at day 1, ×109/L | 4.6 (3.1; 6.9) | 3.7 (2.7; 5.5) | 5.1 (3.8; 8.7) | <.001 |
| Neutrophils at day 3, ×109/L | 4.6 (3.0; 6.8) | 3.7 (2.8; 5.1) | 5.4 (3.6; 9.0) | <.001 |
| Neutrophils at day 5, ×109/L | 4.4 (2.6; 7.4) | 3.3 (2.0; 4.3) | 5.4 (3.5; 10.4) | <.001 |
| Neutrophil-to-lymphocyte ratio at day 1 | 5.8 (3.7; 10.0) | 4.4 (3.0; 7.8) | 7.9 (4.6; 13.3) | <.001 |
| LDH at day 1, U/L | 325 (264; 424) | 283 (240; 347) | 379 (304; 488) | <.001 |
| LDH at day 3, U/L | 334 (263; 440) | 294 (232; 353) | 384 (304; 473) | <.001 |
| Creatinine at day 1, mg/dL | 0.9 (0.7;1.1) | 0.8 (0.7;1.0) | 0.9 (0.7; 1.2) | .034 |
| Platelets at day 1, ×109/L | 182 (135; 232) | 170 (132; 213) | 193 (135; 244) | .072 |
| White blood cell counts at day 1, ×109/L | 5.8 (4.2; 8.2) | 5.1 (3.9; 7.0) | 6.4 (4.7; 10.0) | <.001 |
| White blood cell counts at day 3, ×109/L | 5.6 (4.5; 8.6) | 5.1 (4.1; 6.8) | 7.0 (4.8; 9.9) | <.001 |
| Troponin at day 1, ng/L | 9.7 (3.6; 21.8) | 4.8 (2.7; 16.6) | 12.4 (4.4; 32.0) | .006 |
| Alanine aminotransferase at day 1, U/L | 34 (21; 55) | 30 (19; 47) | 39 (21; 61) | .056 |
| Alanine aminotransferase at day 3, U/L | 35 (25; 61) | 31 (18; 51) | 46 (26; 68) | .008 |
| D-dimer at day 1, ng/mL | 700 (400; 1300) | 500 (300; 1000) | 800 (500; 1900) | <.001 |
| D-dimer at day 3, ng/mL | 776 (400; 1400) | 500 (400; 800) | 1.000 (600; 2200) | <.001 |
| Ferritin at day 1, ng/mL | 749 (321; 1370) | 358 (218; 874) | 971 (468; 1594) | <.001 |
| Ferritin at day 3, ng/mL | 616 (321; 1232) | 474 (270; 929) | 955 (486; 1750) | .004 |
| Oxyhemoglobin saturation, %, median (IQR) | 96 (93; 97) | 97 (95; 98) | 95 (92; 97) | <.001 |
| Ratio of partial pressure of oxygen in arterial blood to the inspired oxygen fraction, median (IQR) | 255 (158; 340) | 281 (205; 326) | 245 (146; 352) | .323 |
| Lopinavir/ritonavir plus hydroxychloroquine, n (%) | 205 (94) | 102 (96) | 103 (93) | .269 |
| Pneumonia severity index, median (IQR) | 69 (48; 96) | 62 (44; 90) | 76 (53; 99) | .019 |
| Severe CAP, n (%) | 85 (40) | 16 (17) | 69 (59) | <.001 |
| Multilobar, n (%) | .013 | |||
| Localized | 72 (32) | 45 (41) | 27 (23) | .003 |
| Unilateral | 13 (6) | 5 (5) | 8 (7) | .468 |
| Bilateral | 141 (62) | 59 (54) | 82 (70) | .013 |
| Acute respiratory distress syndrome, n (%) | 69 (32) | 1 (1) | 68 (59) | <.001 |
| Shock, n (%) | 10 (5) | 0 (0) | 10 (9) | .002 |
| Pulmonary thromboembolism, n (%) | 8 (4) | 1 (1) | 7 (7) | .066 |
| Mechanical ventilation, n (%) | <.001 | |||
| Non-invasive | 18 (8) | 0 (0) | 18 (14) | <.001 |
| Invasive | 57 (24) | 0 (0) | 57 (46) | <.001 |
| Length of hospital stay, days, median (IQR) | 13 (8; 21) | 9 (6; 14) | 19 (12; 34) | <.001 |
| Hospital discharge, n (%) | 190 (79) | 99 (86) | 91 (73) | .011 |
| In-hospital mortality, n (%)d | 26 (12) | 6 (6) | 20 (18) | .007 |
| Panel B | |||
|---|---|---|---|
| ICU Admissiona,e,f,g | Multivariableh |
||
| Variable | OR | 95% CI | P Value |
| Body mass index: Overweight (≥25 and <30 kg/m2) or obese (≥30 kg/m2) |
2.61 | 1.31–5.20 | .006 |
| C-reactive protein-to-lymphocyte ratio at day 1 (+ 10 units)i | 1.05 | 1.02–1.07 | <.001 |
| Ferritin at day 1 (+100 ng/mL)j | 1.05 | 1.02–1.08 | .002 |
| Mechanical Ventilationk,f,g | Non-invasive | Invasive | ||||
|---|---|---|---|---|---|---|
| Multivariablel |
Multivariablel |
|||||
| Variable | OR | 95% CI | P Value | OR | 95% CI | P Value |
| C-reactive protein-to-lymphocyte ratio at day 1 (+ 10 units)i | 1.02 | 0.99–1.05 | .219 | 1.04 | 1.02–1.06 | <.001 |
| Platelets at day 1 (+10 × 109/L)m | 1.09 | 1.03–1.15 | .001 | 1.02 | 0.98–1.06 | .338 |
| Ferritin at day 1 (+100 ng/mL)j | 1.02 | 0.97–1.07 | .531 | 1.06 | 1.03–1.10 | <.001 |
Abbreviations: CAP, community-acquired pneumonia; CI indicates confidence interval; ICU, intensive care unit; IQR, interquartile range; LDH, lactate dehydrogenase; OR, odds ratio; SD, standard deviation.
ICU admission includes direct ICU admission and transfer to ICU in the first 96 h.
Categorical variables were compared using the Chi-squared test or Fisher's exact test. Continuous variables were compared using the t-test or nonparametric Mann–Whitney test. The level of significance was set at 0.05 (two-tailed).
May have more than 1 comorbid condition.
Calculated only for 213 patients who did not have a DNR, died prior to 15 May 2020 or were alive at discharge (102 in the non-ICU group and 111 in the ICU group), i.e. excluding patients who were still hospitalized or with a DNR. Five patients who died in less than 24 h of admission were excluded.
Data is shown as estimated ORs (95% CIs) of the explanatory variables in the ICU group. The OR represents the odds that ICU admission will occur given exposure to the explanatory variable, compared to the odds of the outcome occurring in the absence of such exposure. P-values are based on the null hypothesis that all ORs relating to an explanatory variable equal unity (no effect).
We used the multiple imputation method for missing data in the univariate and multivariable analyses.
The variables analyzed in the univariate analysis were age, gender, body mass index, comorbidity, duration of onset of symptoms to hospital admission, C-reactive protein at day 1, lymphocytes at day 1, C-reactive protein-to-lymphocyte ratio at day 1, neutrophils at day 1, neutrophil-to-lymphocyte ratio at day 1, LDH at day 1, LDH-to-lymphocyte ratio at day 1, platelets at day 1, D-dimer at day 1, and ferritin at day 1. Factors showing an association in the univariate analyses (P < .25) were incorporated in the multivariable model. Final variable selection was performed using the backward stepwise selection method (likelihood ratio) (Pin < 0.05, Pout > 0.10). Single collinearity was evaluated using the Pearson correlation (r); multicollinearity was examined by means of the variance inflation factor (VIF).
Hosmer–Lemeshow goodness-of-fit test for the multivariable model, P = .603. Area under the ROC curve for the multivariable model, AUC = 0.77 (95% CI 0.71–0.83). Linear relationships between continuous predictors and logit (log odds) were confirmed by the Box-Tidwell test. Internal validation of the multivariable model using ordinary nonparametric bootstrapping with 1000 samples demonstrated robust results for the three variables included in the model, with small 95% CIs around the original coefficients.
“+10 units” indicates an increase by ten units.
“+100 ng/mL” indicates an increase by one hundred ng/mL.
Data is shown as estimated ORs (95% CIs) of the explanatory variables in non-invasive mechanical ventilation and invasive mechanical ventilation groups. The OR represents the odds that the need for non-invasive mechanical ventilation or invasive mechanical ventilation will occur given exposure to the explanatory variable, compared to the odds of the outcome occurring in the absence of such exposure. P-values are based on the null hypothesis that all ORs relating to an explanatory variable equal unity (no effect).
Model characteristics: likelihood ratio Chi-squared test, P = .637; R2 coefficients = 0.24 (Cox and Snell), 0.30 (Nagelkerke). AUC = 0.73 (95% CI 0.61–0.85) for non-invasive mechanical ventilation group and AUC = 0.80 (95% CI 0.74–0.87) for invasive mechanical ventilation group. Linear relationships between continuous predictors and logit (log odds) were confirmed with the Box-Tidwell test. Internal validation of the multivariable model using ordinary nonparametric bootstrapping with 1000 samples demonstrated robust results for the three variables included in the model, with small 95% CIs around the original coefficients.
“+10 × 109/L” indicates an increase by ten ×109/L.