Demographic and clinical characteristics of the study population
A total of 326 participants (43.87% males, 61.22 ± 0.86 years old) with SARS-CoV-2 were finally included in this study. Baseline characteristics of the patients were divided into two groups according to the cut-off value determined in ROC curve: high-SII group (136cases, 36.76%, 66.43 ± 1.09 years old) and low-SII group (190cases, 48.95% males, 57.49 ± 1.18 years old).
In Table 1, diabetes mellitus was the most common comorbidity in high-SII group, followed by hypertension and coronary heart disease. The common symptoms on admission presented the significant differences between two groups in dyspnea (75.74% vs 47.37%, P < 0.001), chest distress (37.50% vs 15.26%, P < 0.001), chest pain (12.50% vs 3.68%, P = 0.003) and consciousness disorders (8.09% vs 2.11%, P = 0.011). Most high-SII group patients used arbidol for antiviral therapy and the difference was statistically significant (62.50% vs 26.84%, P < 0.001). Followed by oseltamivir (2.94% vs 1.58%, P = 0.403) and lopinavir/ritonavir (5.15% vs 4.21%, P = 0.691). Meanwhile, low-SII group patients received most combined antiviral therapy (40.53% vs 26.47%, P = 0.008). More people in high-SII group were treated with glucocorticoids (GCS) (P < 0.001) and immune globulin (P = 0.002). The application of oxygen therapy (noninvasive mechanical ventilation and invasive mechanical ventilation) and continuous renal replace therapy were adopted more in high-SII group patients (P < 0.001, respectively). Furthermore, we found that patients in high-SII group with a higher chance of severe complications, such as multiple organ dysfunction syndrome, ARDS, major cardiovascular adverse events, disseminated intravascular coagulation, secondary infection, sepsis-shock and acidosis (P < 0.001, respectively).
Table 1
Demographics and clinical characteristics of study population
| All patients (n = 326) | SII < 1293.11 (n = 190) | SII ≥ 1293.11 (n = 136) | P |
Gender, (male), n (%) | 143 (43.87%) | 93 (48.95%) | 50 (36.76%) | 0.029 |
Age, year | 61.22 ± 0.86 | 57.49 ± 1.18 | 66.43 ± 1.09 | < 0.001 |
Smoking, n (%) | 41 (12.58%) | 11 (5.79%) | 30 (22.06%) | < 0.001 |
Comorbidity, n (%) |
CHD | 46 (14.11%) | 15 (7.89%) | 31 (22.79%) | < 0.001 |
Hypertension | 115 (35.28%) | 54 (28.42%) | 61 (44.85%) | 0.002 |
Diabetes | 111 (34.05%) | 45 (23.68%) | 66 (48.53%) | < 0.001 |
Chronic lung disease | 26 (7.98%) | 11 (5.79%) | 15 (11.03%) | 0.085 |
Chronic kidney disease | 8 (2.45%) | 4 (2.11%) | 4 (2.94%) | 0.631 |
Chronic liver disease | 14 (4.29%) | 9 (4.74%) | 5 (3.68%) | 0.641 |
Autoimmune diseases | 8 (2.45%) | 6 (3.16%) | 2 (1.47%) | 0.332 |
Tumor | 19 (5.83%) | 14 (7.37%) | 5 (3.68%) | 0.161 |
Cerebrovascular disease | 17 (5.21%) | 8 (4.21%) | 9 (6.62%) | 0.335 |
Gastrointestinal disease | 16 (4.91%) | 6 (3.16%) | 10 (7.35%) | 0.084 |
Time of illness onset, days | 10.81 ± 0.34 | 10.14 ± 0.42 | 11.75 ± 0.55 | 0.018 |
Hospital admission, days | 14.50 ± 0.42 | 16.21 ± 0.51 | 12.10 ± 0.66 | < 0.001 |
Initial common symptoms, n (%) |
Fever | 288(88.34%) | 171 (90.00%) | 117 (86.03%) | 0.271 |
Cough | 191(58.59%) | 121 (63.68%) | 70 (51.47%) | 0.027 |
Sputum | 121(37.12%) | 68 (35.79%) | 53 (38.97%) | 0.558 |
Pharyngalgia | 19 (5.83%) | 11 (5.79%) | 8 (5.88%) | 0.932 |
Dyspnea | 193(59.20%) | 90 (47.37%) | 103 (75.74%) | < 0.001 |
Fatigue | 148(45.40%) | 76 (40.00%) | 72 (52.94%) | 0.021 |
Myalgia | 97 (29.75%) | 55 (28.95%) | 42 (30.88%) | 0.706 |
Stomachache | 31 (9.51%) | 17 (8.95%) | 14 (10.29%) | 0.683 |
Anorexia | 92 (28.22%) | 49 (25.79%) | 43 (31.62%) | 0.249 |
Diarrhea | 103(31.60%) | 61 (32.11%) | 42 (30.88%) | 0.815 |
Disgusting vomits | 47 (14.42%) | 30 (15.79%) | 17 (12.50%) | 0.404 |
Chest distress | 80 (24.54%) | 29 (15.26%) | 51 (37.50%) | < 0.001 |
Chest pain | 24 (7.36%) | 7 (3.68%) | 17 (12.50%) | 0.003 |
Palpitation | 32 (9.82%) | 14 (7.37%) | 18 (13.24%) | 0.079 |
Dizziness | 32 (9.82%) | 19 (10.00%) | 13 (9.56%) | 0.895 |
Headache | 61 (18.71%) | 34 (17.89%) | 27 (19.85%) | 0.655 |
Consciousness disorders | 15 (4.60%) | 4 (2.11%) | 11 (8.09%) | 0.011 |
Temperature, ℃ | 37.36 ± 0.05 | 37.23 ± 0.07 | 37.55 ± 0.09 | < 0.001 |
SBP (mmHg) | 129.98 ± 1.20 | 127.95 ± 1.56 | 132.81 ± 1.84 | 0.042 |
DBP (mmHg) | 81.56 ± 1.87 | 79.71 ± 1.19 | 84.12 ± 4.14 | 0.242 |
HR (beats/min) | 96.43 ± 1.09 | 94.66 ± 1.38 | 98.89 ± 1.76 | 0.083 |
SPO2, % | 90.30 ± 0.62 | 94.19 ± 0.49 | 85.16 ± 1.15 | < 0.001 |
Pharmacotherapy in hospital, n (%) |
Antibiotic therapy | 301(92.33%) | 171 (90.00%) | 130 (95.59%) | 0.062 |
Antiviral therapy | | | | |
Arbidol | 136 (56.44%) | 51 (26.84%) | 85 (62.50%) | < 0.001 |
Oseltamivir | 7 (2.15%) | 3 (1.58%) | 4 (2.94%) | 0.403 |
Lopinavir and Ritonavir | 15 (4.60%) | 8 (4.21%) | 7 (5.15%) | 0.691 |
Combined antiviral therapy | 113 (34.66%) | 77 (40.53%) | 36 (26.47%) | 0.008 |
Interferon therapy | 91 (27.91%) | 55 (28.95%) | 36 (26.47%) | 0.623 |
ACEI/ARB | 9 (2.76%) | 6 (3.16%) | 3 (2.21%) | 0.605 |
GCS | 224 (68.71%) | 108 (56.84%) | 116 (85.29%) | < 0.001 |
Days of GCS use, days | 4.82 ± 0.31 | 4.02 ± 0.38 | 5.93 ± 0.49 | 0.001 |
Immune globulin | 130 (39.88%) | 62 (32.63%) | 68 (50.00%) | 0.002 |
Oxygen therapy in hospital, n (%) | |
NMV | 155 (47.55%) | 57 (30.00%) | 98 (72.06%) | < 0.001 |
IMV | 86 (26.38%) | 21 (11.05%) | 65 (47.79%) | < 0.001 |
Time of starting IMV, days | 1.79 ± 0.22 | 0.82 ± 0.21 | 3.15 ± 0.41 | < 0.001 |
Other treatment in hospital, n (%) |
CRRT | 19 (5.83%) | 5 (2.63%) | 14 (10.29%) | 0.004 |
Time of starting CRRT, days | 0.75 ± 0.19 | 0.24 ± 0.11 | 1.47 ± 0.41 | < 0.001 |
ECMO | 5 (1.53%) | 2 (1.05%) | 3 (2.21%) | 0.403 |
Time of starting ECMO, days | 0.15 ± 0.09 | 0.09 ± 0.08 | 0.24 ± 0.19 | 0.013 |
Complications, n (%) |
Death | 147 (45.09%) | 45 (23.68%) | 102 (75.00%) | < 0.001 |
MODS | 139 (42.64%) | 43 (22.63%) | 96 (70.59%) | < 0.001 |
ARDS | 116 (35.58%) | 38 (20.00%) | 78 (57.35%) | < 0.001 |
DIC | 75 (23.01%) | 24 (12.63%) | 51 (37.50%) | < 0.001 |
Secondary infection | 42 (12.88%) | 13 (6.84%) | 29 (21.32%) | < 0.001 |
MACE | 81 (24.85%) | 21 (11.05%) | 60 (44.12%) | < 0.001 |
VMC | 41 (12.58%) | 11 (5.79%) | 30 (22.06%) | < 0.001 |
AKI | 53 (16.26%) | 17 (8.95%) | 36 (26.47%) | < 0.001 |
Rhabdomyolysis | 7 (2.15%) | 1 (0.53%) | 6 (4.41%) | 0.017 |
Spesis shock | 52 (15.95%) | 15 (7.89%) | 37 (27.21%) | < 0.001 |
Myelosuppression | 79 (24.23%) | 23 (12.11%) | 56 (41.18%) | < 0.001 |
Acidosis | 64 (19.63%) | 13 (6.84%) | 51 (37.50) | < 0.001 |
Low T3 syndrome | 15 (4.60%) | 2 (1.05%) | 13 (9.56%) | < 0.001 |
Cerebrovascular accident | 5 (1.53%) | 3 (1.58%) | 2 (1.47%) | 0.937 |
GIB | 14 (4.29%) | 5 (2.63%) | 9 (6.62%) | 0.080 |
Liver function impairment | 81 (24.85%) | 33 (17.37%) | 48 (35.29%) | < 0.001 |
Pneumothorax | 9 (2.76%) | 3 (1.58%) | 6 (4.41%) | 0.124 |
Abbreviations: Mean ± SEM and n (%) are reported for continuous and categorical variables, respectively. SEM – standard error of the mean. SII systemic immune-inflammation index, CHD coronary heart disease, SBP systolic blood pressure, DBP diastolic blood pressure, HR heart rate, SPO2 surplus pulse O2, ACEI/ARB angiotensin-converting enzyme inhibitor / angiotensin II receptor blocker, GCS glucocorticoid, NMV noninvasive mechanical ventilation; IMV invasive mechanical ventilation; CRRT continuous renal replacement therapy, ECMO extracorporeal membrane oxygenation, MODS multiple organ dysfunction syndrome, ARDS acute respiratory distress syndrome, DIC disseminated intravascular coagulation, MACE major adverse cardiac events, VMC viral myocarditis, AKI acute kidney injury, GIB gastrointestinal bleeding |
Laboratory and radiological imaging findings
As shown in Table 2, blood routine tests showed that the levels of white blood cell count, neutrophil, neutrophil%, monocyte%, hemoglobin and platelet were higher in high-SII group compared with low-SII group (P < 0.001, respectively). On the contrary, the lymphocyte value and lymphocyte% value were much lower in high-SII group (P < 0.001, respectively). Biochemical examining reports indicated that there was significant difference in cardiac parameters, liver function index, renal function index between the two groups (P < 0.001, respectively). The patients in high-SII group were more likely to have higher concentration of immuno-inflammatory indices (such as high-sensitivity C-reactive protein, ferritin,procalcitonin, cytokines etc.) (P < 0.001, respectively). Besides, there were also significant differences in blood coagulation function between the two groups (P < 0.050), except for fibrinogen.
Table 2
Laboratory, and radiographic characteristics of study population
| All patients (n = 326) | SII < 1293.11 (n = 190) | SII ≥ 1293.11 (n = 136) | P |
Blood routine index, 109/L |
WBC, 109/L | 7.55 ± 0.27 | 5.16 ± 0.18 | 10.90 ± 0.46 | < 0.001 |
Neutrophil%, % | 75.95 ± 0.83 | 67.10 ± 0.96 | 88.32 ± 0.48 | < 0.001 |
Neutrophil, 109/L | 6.21 ± 0.27 | 3.65 ± 0.18 | 9.79 ± 0.45 | < 0.001 |
Lymphocyte%, % | 16.14 ± 0.63 | 22.88 ± 0.74 | 6.73 ± 0.33 | < 0.001 |
Lymphocyte, 109/L | 0.90 ± 0.04 | 1.11 ± 0.06 | 0.61 ± 0.03 | < 0.001 |
Monocyte%, % | 6.87 ± 0.22 | 8.48 ± 0.29 | 4.63 ± 0.23 | < 0.001 |
Monocyte, 109/L | 0.47 ± 0.02 | 0.43 ± 0.02 | 0.47 ± 0.03 | 0.291 |
Hemoglobin, mg/dL | 124.74 ± 1.33 | 122.19 ± 1.75 | 128.30 ± 2.01 | 0.027 |
Platelet, 109/L | 194.05 ± 5.03 | 183.87 ± 6.53 | 208.06 ± 7.73 | < 0.001 |
Coagulation function |
PT, sec | 15.32 ± 0.33 | 15.09 ± 0.55 | 15.64 ± 0.22 | < 0.001 |
PTA, % | 87.09 ± 3.03 | 93.98 ± 5.04 | 77.56 ± 1.52 | < 0.001 |
FIB, g/L | 4.90 ± 0.10 | 4.74 ± 0.12 | 5.13 ± 0.19 | 0.110 |
APTT, sec | 42.23 ± 0.75 | 43.80 ± 1.17 | 40.04 ± 0.66 | 0.012 |
D-dimer, ug/mL FEU | 4.78 ± 0.41 | 2.59 ± 0.38 | 7.92 ± 0.75 | < 0.001 |
FDP, ug/mL | 30.46 ± 3.85 | 15.30 ± 3.47 | 51.76 ± 7.15 | < 0.001 |
Biochemical indexes |
CTnI, pg/ml | 604.50 ± 195.76 | 511.62 ± 191.65 | 712.21 ± 360.45 | < 0.001 |
NT-proBNP, pg/ml | 2420.50 ± 511.69 | 1420.68 ± 432.13 | 3532.36 ± 960.08 | < 0.001 |
ALT, u/L | 37.25 ± 3.49 | 36.74 ± 5.69 | 37.96 ± 2.72 | < 0.001 |
AST (u/L) | 47.97 ± 5.32 | 47.69 ± 8.90 | 48.34 ± 3.06 | < 0.001 |
Albumin, g/L | 33.31 ± 0.30 | 35.22 ± 0.37 | 30.67 ± 0.41 | < 0.001 |
Globulin, g/L | 34.14 ± 0.35 | 32.86 ± 0.49 | 35.09 ± 0.47 | < 0.001 |
TBiL, umol/L | 15.68 ± 2.23 | 13.46 ± 2.74 | 18.76 ± 3.74 | < 0.001 |
TC, mmol/l | 3.57 ± 0.05 | 3.61 ± 0.07 | 3.51 ± 0.08 | 0.288 |
TG, mmol/L | 1.65 ± 0.07 | 1.54 ± 0.12 | 1.77 ± 0.08 | < 0.001 |
HDL-C, mmol/l | 0.85 ± 0.02 | 0.93 ± 0.03 | 0.76 ± 0.03 | < 0.001 |
LDL-C, mmol/l | 2.18 ± 0.06 | 2.21 ± 0.07 | 2.15 ± 0.11 | 0.653 |
CK, u/L | 253.06 ± 37.77 | 209.91 ± 37.50 | 304.14 ± 69.40 | < 0.001 |
LDH, u/L | 425.99 ± 16.16 | 351.32 ± 20.14 | 529.97 ± 23.98 | < 0.001 |
Potassium, mmol/L | 4.31 ± 0.04 | 4.22 ± 0.04 | 4.43 ± 0.06 | 0.003 |
Sodium, mmol/L | 140.08 ± 0.34 | 140.10 ± 0.41 | 140.05 ± 0.57 | 0.846 |
Calcium, mmol/L | 2.36 ± 0.01 | 2.34 ± 0.02 | 2.38 ± 0.02 | 0.082 |
Urea, mmol/L | 7.67 ± 0.44 | 6.34 ± 0.62 | 9.52 ± 0.58 | < 0.001 |
Creatinine, mmol/L | 95.16 ± 4.95 | 89.83 ± 5.79 | 102.57 ± 8.65 | < 0.001 |
eGFR, ml/min/1.73 m2/L | 82.35 ± 1.52 | 87.98 ± 1.99 | 74.46 ± 2.17 | < 0.001 |
HCO3−, mmol/L | 22.85 ± 0.19 | 23.46 ± 0.24 | 21.99 ± 0.32 | < 0.001 |
Immuno-inflammatory indices |
Hs-CRP, mg/L | 76.31 ± 3.95 | 53.29 ± 4.27 | 108.15 ± 6.38 | < 0.001 |
ESR, mm/H | 38.78 ± 1.55 | 33.38 ± 1.92 | 45.95 ± 2.42 | 0.024 |
Ferritin, ug/L | 1483.87 ± 188.08 | 1404.84 ± 305.74 | 1598.54 ± 127.02 | < 0.001 |
PCT, ng/mL | 1.39 ± 0.47 | 1.051 ± 0.49 | 1.90 ± 0.89 | < 0.001 |
Ig A, g/L | 2.40 ± 0.09 | 2.27 ± 0.11 | 2.57 ± 0.15 | 0.106 |
Ig G, g/L | 12.43 ± 0.29 | 11.95 ± 0.37 | 13.07 ± 0.47 | 0.061 |
Ig M, g/L | 1.06 ± 0.04 | 1.07 ± 0.06 | 1.05 ± 0.07 | 0.462 |
Alexin C3, g/L | 0.83 ± 0.02 | 0.86 ± 0.02 | 0.80 ± 0.02 | 0.046 |
Alexin C4, g/L | 0.24 ± 0.01 | 0.26 ± 0.01 | 0.21 ± 0.01 | < 0.001 |
IL-1β, pg/ml | 5.93 ± 0.26 | 5.83 ± 0.25 | 6.08 ± 0.54 | 0.313 |
IL-2R, pg/ml | 1008.15 ± 51.85 | 829.88 ± 65.14 | 1267.62 ± 78.46 | < 0.001 |
IL-6, pg/ml | 113.32 ± 31.35 | 78.74 ± 34.47 | 163.64 ± 58.25 | < 0.001 |
IL-8, pg/ml | 68.94 ± 30.36 | 32.12 ± 4.93 | 122.55 ± 74.10 | < 0.001 |
IL-10, pg/ml | 12.44 ± 1.25 | 10.12 ± 0.90 | 15.81 ± 2.76 | < 0.001 |
TNF-α, pg/ml | 11.70 ± 0.63 | 11.24 ± 0.83 | 12.36 ± 0.98 | < 0.001 |
Pathogen infection, n (%) |
Influenza virus A | 66 (20.25%) | 37 (19.47%) | 29 (21.32%) | 0.682 |
Influenza virus B | 14 (4.29%) | 7 (3.68%) | 7 (5.15%) | 0.521 |
Sendai virus | 3 (0.92%) | 2 (1.05%) | 1 (0.74%) | 0.767 |
Mycoplasma | 2 (0.61%) | 2 (1.05%) | 0 (0.00%) | 0.230 |
Chlamydia | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | NA |
Adenovirus | 1 (0.31%) | 0 (0.00%) | 1 (0.74%) | 0.236 |
Hepatitis B virus | 15 (4.60%) | 8 (4.21%) | 7 (5.15%) | 0.698 |
Hepatitis C virus | 4 (1.23%) | 2 (1.05%) | 2 (1.47%) | 0.735 |
HIV | 1 (0.31%) | 0 (0.00%) | 1 (0.74%) | 0.236 |
Syphilis | 4 (1.23%) | 2 (1.05%) | 2 (1.47%) | 0.735 |
Co-infection | 14 (4.29%) | 11 (5.79%) | 3 (2.21%) | 0.116 |
Radiographic findings, n(%) |
Unilateral pneumonia | 9 (2.76%) | 8 (4.21%) | 1 (0.74%) | 0.058 |
Bilateral pneumonia | 200 (61.35%) | 115 (60.53%) | 85 (62.50%) | 0.718 |
Hydrothorax | 18 (5.52%) | 10 (5.26%) | 8 (5.88%) | 0.809 |
Ground-glass opacity | 176 (53.99%) | 107 (56.32%) | 69 (50.74%) | 0.319 |
Consolidation | 15 (4.60%) | 8 (4.21%) | 7 (5.15%) | 0.698 |
MuLBTSA score | 7.87 ± 0.21 | 7.75 ± 0.25 | 8.02 ± 0.35 | 0.009 |
Mean ± SEM and n (%) are reported for continuous and categorical variables, respectively. NA-not available. Abbreviations: SII systemic immune-inflammation index, WBC white blood cell count, PT prothrombin time, PTA prothrombin activity, FIB fibrinogen, APTT activated partial thromboplastin time, FDP fibrinogen degradation product, CTnI cardiac troponin I, NT-proBNP N-terminal pro brain natriuretic peptide, AST aspartate aminotransferase, ALT alanine aminotransferase, TBiL total bilirubin, TC total cholesterol, TG triglyceride, HDL-C high density lipoprotein cholesterol, LDL-C low density lipoprotein cholesterol, CK creatine kinase, LDH lactate dehydrogenase, eGFR estimated glomerular filtration rate, HCO3− bicarbonate ion, Hs-CRP high-sensitivity C-reactive protein, ESR erythrocyte sedimentation rate, PCT procalcitonin, Ig A immunoglobulin A, Ig G immunoglobulin G, Ig M immunoglobulin M, IL-1β interleukin-1, IL-2R interleukin-2 receptor, IL-6 interleukin-6, IL-8 interleukin-8, IL-10 interleukin-10, TNF-α tumor necrosis factor α, HIV human immunodeficiency virus |
ROC curve analysis
To clarify the factors that affect COVID-19 prognosis, the ROC curves was used to analyze the prognostic value. The optimized cut-off point of SII value for predicting in-hospital death was 1293.11 with the sensitivity for 69.90% and the specificity for 70.80%. The area under the curve (AUC) for death was 0.789 (95%CI = 0.739–0.840, P < 0.001) (Fig. 1A). Besides, in our cohort study, SII was a significantly stronger predictor of in-hospital mortality than MuLBSTA score (AUC = 0.585, 95%CI = 0.521–0.648, P = 0.009), The sensitivity and the specificity of SII was also improved than MuLBSTA score (sensitivity = 38.40% ,and the specificity = 80.80%) (Fig. 1A).
The best cut-off point of SII value for predicting the development of ARDS was also 1293.11, with the sensitivity for 67.80% and the specificity for 71.10%. The AUC for developing ARDS was 0.736 (95%CI = 0.679–0.794, P < 0.001) (Fig. 1B).
Survival analysis
The mean length of hospitalization in patients with COVID-19 was 14.50 ± 0.42 days (range from 1–33 days). In total, 147 (45.09%) people died and 116 (35.58%) patients developed ARDS during hospitalization. Kaplan-Meier survival curves show that patients with higher SII level had significantly worse in-hospital outcomes than those with lower SII level (log-rank test, all p values were < 0.001) (Fig. 2).
In our study, 86 (26.38%) people with respiratory failure were given invasive ventilation. The mean time for patients starting to be given invasive ventilation was 1.79 ± 0.22 days (range from 0–19 days). Kaplan-Meier survival curves showed that the earlier the invasive ventilation was given, the better the prognosis would be (log-rank test, P < 0.001) (Fig. 3).
Cox regression analysis of the factors associated with the outcomes
As shown in Table 3, the univariate Cox regression analysis showed that the HR of SII associated to in-hospital death was 4.286 (95% CI = 3.004–6.114, P < 0.001). We also evaluated other factors with the outcomes, such as sex, age, smoking history, comorbidities, blood routine index, serum biochemical index, coagulation function, infection-related indices and so on. The multivariate Cox regression analysis indicated that older age (HR = 1.052, 95% CI = 1.018–1.088, P = 0.002), lower albumin levels (HR = 0.912, 95% CI = 0.852–0.975, P = 0.007), lower lymphocyte proportion (HR = 0.857, 95% CI = 0.792–0.927, P < 0.001), higher IL-6 level (HR = 1.002, 95% CI = 1.001–1.004, P = 0.043), and higher SII level (≥ 1293.11) (HR = 2.839, 95% CI = 1.116–7.222, P = 0.028) were the risk factors for in-hospital death. Meanwhile, the treatment with glucocorticoid (HR = 0.200, 95% CI = 0.059–0.671, P = 0.009) was associated with lower risk of in-hospital death.
Table 3
Predictors of in-hospital mortality in univariable and multivariable Cox regression analyses.
Variables | Univariable | Multivariable |
HR | 95% CI | p | | HR | 95% CI | p |
Age | 1.611 | 1.146–2.264 | 0.006 | 1.052 | 1.018–1.088 | 0.002 |
Gender (male) | 2.582 | 1.735–3.841 | < 0.001 | | | |
Smoking | 2.451 | 1.674–3.588 | < 0.001 | | | |
Comorbidity |
CHD | 1.776 | 1.175–2.684 | 0.006 | | | |
Hypertension | 2.009 | 1.450–2.782 | < 0.001 | | | |
Diabetes | 2.723 | 1.967–3.770 | < 0.001 | | | |
Time of illness onset | 1.036 | 1.009–1.063 | 0.008 | | | |
The use of GCS | 3.168 | 1.956–5.132 | < 0.001 | 0.200 | 0.059–0.671 | 0.009 |
SII | 4.286 | 3.004–6.114 | < 0.001 | 2.839 | 1.116–7.222 | 0.028 |
Blood routine index |
WBC | 1.134 | 1.109–1.159 | < 0.001 | | | |
Neutrophil | 1.139 | 1.115–1.164 | < 0.001 | | | |
Neutrophil% | 1.096 | 1.077–1.116 | < 0.001 | | | |
Lymphocyte | 0.116 | 0.168–0.199 | < 0.001 | | | |
Lymphocyte% | 0.879 | 0.857–0.902 | < 0.001 | 0.857 | 0.792–0.927 | < 0.001 |
Monocyte | 1.532 | 1.036–2.267 | 0.033 | | | |
Monocyte% | 0.822 | 0.78–0.867 | < 0.001 | | | |
Hemoglobin | 0.993 | 0.987–0.999 | 0.03 | | | |
Platelet | 0.994 | 0.992–0.996 | < 0.001 | | | |
Coagulation function |
PT | 1.036 | 1.024–1.048 | < 0.001 | | | |
D-Dimmer | 1.088 | 1.068–1.108 | < 0.001 | | | |
Biochemical indexes |
ALT | 1.003 | 1.001–1.005 | < 0.001 | | | |
AST | 1.002 | 1.001–1.003 | < 0.001 | | | |
Albumin | 0.872 | 0.845–0.899 | < 0.001 | 0.912 | 0.852–0.975 | 0.007 |
Globulin | 1.018 | 0.997–1.039 | 0.087 | | | |
TBiL | 1.005 | 1.002–1.007 | < 0.001 | | | |
TG | 1.317 | 1.158–1.497 | < 0.001 | | | |
HDL-C | 0.087 | 0.037–0.205 | < 0.001 | | | |
LDL-C | 0.568 | 0.417–0.774 | < 0.001 | | | |
CK | 1.001 | 1.000-1.001 | < 0.001 | | | |
LDH | 1.002 | 1.001–1.002 | < 0.001 | | | |
Creatinine | 1.002 | 1.001–1.003 | < 0.001 | | | |
eGFR | 0.976 | 0.970–0.982 | < 0.001 | | | |
Immuno-inflammatory indices |
Hs-CRP | 1.009 | 1.007–1.011 | < 0.001 | | | |
ESR | 1.006 | 0.999–1.013 | 0.100 | | | |
Ferritin | 5.521 | 3.588–8.497 | < 0.001 | | | |
PCT | 1.027 | 1.015–1.040 | < 0.001 | | | |
Alexin C3 | 0.067 | 0.023–0.190 | < 0.001 | | | |
Alexin C4 | 0.003 | 0.001–0.049 | < 0.001 | | | |
IL-2R | 1.001 | 1.000-1.001 | < 0.001 | | | |
IL-6 | 1.001 | 1.000-1.001 | < 0.001 | 1.002 | 1.001–1.004 | 0.043 |
IL-8 | 1.001 | 1.000-1.001 | < 0.001 | | | |
IL-10 | 1.012 | 1.008–1.017 | < 0.001 | | | |
TNF-α | 1.044 | 1.032–1.056 | < 0.001 | | | |
Abbreviations: HR hazard ratio, CI confidence interval, CHD coronary heart disease, GCS glucocorticoid, NMV noninvasive mechanical ventilation, IMV invasive mechanical ventilation, WBC white blood cell count, PT prothrombin time, ALT alanine aminotransferase, AST aspartate aminotransferase, TBiL total bilirubin, TG triglyceride, HDL-C high density lipoprotein cholesterol, LDL-C low density lipoprotein cholesterol, LDH lactate dehydrogenase, CK creatine kinase, eGFR estimated glomerular filtration rate, Hs-CRP high-sensitivity C-reactive protein, ESR erythrocyte sedimentation rate, PCT procalcitonin, IL-2R interleukin-2 receptor, IL-6 interleukin-6, IL-8 interleukin-8, IL-10 interleukin-10, TNF-α tumor necrosis factor α |
We also evaluated the factors with the outcomes of developed ARDS. The univariate Cox regression analysis showed that the HR of SII associated to the development of ARDS was 3.836 (95% CI = 2.589–5.685, P < 0.001). The multivariate Cox regression analysis indicated that higher SII level (≥ 1293.11) (HR = 6.832, 95% CI = 2.583–18.074, P < 0.001) was the independent risk factors for developing ARDS. Nevertheless, the lymphocyte proportion (HR = 0.776, 95% CI = 0.713–0.845, P < 0.001) was negatively correlated with the risk of the development of ARDS (Table 4).
Table 4
Predictors of developed ARDS in univariable and multivariable Cox regression analyses.
Variables | Univariable | Multivariable |
HR | 95% CI | p | | HR | 95% CI | p |
Age | 3.33 | 2.055–5.398 | < 0.001 | | | |
Gender (male) | 2.541 | 1.255–5.145 | 0.01 | | | |
Smoking | 2.109 | 1.353–3.288 | 0.001 | | | |
Comorbidity |
CHD | 1.666 | 1.036–2.677 | 0.035 | | | |
Hypertension | 2.160 | 1.498–3.115 | < 0.001 | | | |
Diabetes | 2.683 | 1.861–3.868 | < 0.001 | | | |
Time of illness onset | 1.005 | 0.972–1.039 | 0.784 | | | |
The use of GCS | 2.927 | 1.726–4.965 | < 0.001 | | | |
SII | 3.836 | 2.589–5.685 | < 0.001 | 6.832 | 2.583–18.074 | < 0.001 |
Blood routine index |
WBC | 1.131 | 1.103–1.160 | < 0.001 | | | |
Neutrophil | 1.137 | 1.110–1.166 | < 0.001 | | | |
Neutrophil% | 1.099 | 1.077–1.122 | < 0.001 | | | |
Lymphocyte | 0.103 | 0.056–0.190 | < 0.001 | | | |
Lymphocyte% | 0.877 | 0.852–0.904 | < 0.001 | 0.776 | 0.713–0.845 | < 0.001 |
Monocyte | 1.404 | 0.868–2.270 | 0.167 | | | |
Monocyte% | 0.808 | 0.761–0.859 | < 0.001 | | | |
Hemoglobin | 0.992 | 0.985–0.999 | 0.020 | | | |
Platelet | 0.993 | 0.991–0.996 | < 0.001 | | | |
Coagulation function |
PT | 1.036 | 1.023–1.050 | < 0.001 | | | |
D-Dimmer | 1.083 | 1.061–1.106 | < 0.001 | | | |
Biochemical indexes |
ALT | 1.003 | 1.001–1.005 | 0.016 | | | |
AST | 1.002 | 1.001–1.003 | < 0.001 | | | |
Albumin | 0.883 | 0.853–0.914 | < 0.001 | | | |
Globulin | 1.012 | 0.987–1.037 | 0.362 | | | |
TBiL | 1.005 | 1.002–1.007 | < 0.001 | | | |
TG | 1.343 | 1.165–1.548 | < 0.001 | | | |
HDL-C | 0.125 | 0.047–0.334 | < 0.001 | | | |
LDL-C | 0.574 | 0.402–0.820 | 0.002 | | | |
CK | 1.001 | 1.000-1.001 | 0.012 | | | |
LDH | 1.002 | 1.001–1.002 | < 0.001 | | | |
CR | 1.002 | 1.001–1.003 | < 0.001 | | | |
eGFR | 0.974 | 0.968–0.980 | < 0.001 | | | |
Immuno-inflammatory indices |
Hs-CRP | 1.009 | 1.007–1.010 | < 0.001 | | | |
ESR | 1.002 | 0.994–1.010 | 0.606 | | | |
Ferritin | 6.967 | 3.677–13.200 | < 0.001 | | | |
PCT | 1.029 | 1.017–1.042 | < 0.001 | | | |
Alexin C3 | 0.057 | 0.017–0.192 | < 0.001 | | | |
Alexin C4 | 0.003 | 0.001–0.070 | < 0.001 | | | |
IL-2R | 1.001 | 1.000-1.001 | < 0.001 | | | |
IL-6 | 1.001 | 1.000-1.001 | < 0.001 | | | |
IL-8 | 1.001 | 1.000-1.001 | 0.005 | | | |
IL-10 | 1.013 | 1.008–1.018 | < 0.001 | | | |
TNF-α | 1.047 | 1.034–1.060 | < 0.001 | | | |
Abbreviations: ARDS acute respiratory distress syndrome,HR hazard ratio༌CI confidence interval༌CHD coronary heart disease༌GCS glucocorticoid༌NMV noninvasive mechanical ventilation༌IMV invasive mechanical ventilation༌WBC white blood cell count༌PT prothrombin time༌ALT alanine aminotransferase༌AST aspartate aminotransferase༌TBiL total bilirubin༌TG triglyceride༌HDL-C high density lipoprotein cholesterol༌LDL-C low density lipoprotein cholesterol༌LDH lactate dehydrogenase༌CK creatine kinase༌eGFR estimated glomerular filtration rate༌Hs-CRP high-sensitivity C-reactive protein༌ESR erythrocyte sedimentation rate༌PCT procalcitonin༌IL-2R interleukin-2 receptor༌IL-6 interleukin-6༌IL-8 interleukin-8༌IL-10 interleukin-10༌TNF-α tumor necrosis factor α |
The dynamic changes of SII in study population
The dynamic change of SII value in-hospital was described in Fig. 4. The SII level on admission was generally lower than that before discharge and there was significantly different between two groups (survival group P = 0.002, dead group P = 0.016). Similar findings were seen in the non-ARDS group patients (P < 0.001). It suggested that the changes of the value of SII was correlated with the outcomes to some extent.