Abstract
Objective: The De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) has emerged as a prognostic biomarker in critical illness. This study aimed to evaluate the independent prognostic value of the De Ritis ratio for ICU mortality in critically ill patients with COVID-19. Methods: This retrospective observational cohort study was conducted at a single tertiary center. Medical records of 642 adult patients with RT-PCR–confirmed COVID-19 admitted to the Internal Medicine ICU between January and December 2021 were reviewed. Demographic data, comorbidities, laboratory parameters, severity scores (APACHE II and SOFA), and organ support requirements were recorded at ICU admission. Patients were stratified into survivor and non-survivor subgroups. Independent predictors of ICU mortality were identified through two multivariable logistic regression models. Discriminative performance was assessed by receiver operating characteristic curve analysis. Results: ICU mortality was recorded in 341 patients (53.1%). Non-survivors were significantly older and had markedly elevated inflammatory biomarkers, D-dimer, urea, and De Ritis ratio values. Although absolute AST and ALT concentrations did not differ significantly between groups, the De Ritis ratio was independently associated with ICU mortality in both models (Model A: OR 1.27, 95% CI 1.06–1.51, p = 0.009; Model B: OR 1.26, 95% CI 1.05–1.50, p = 0.013). Combining the De Ritis ratio with severity scores improved discriminative performance (AUC up to 0.661). Conclusion: The De Ritis ratio at ICU admission was independently associated with mortality in critically ill COVID-19 patients and provided additional prognostic information beyond established severity scores. Given its modest discriminative performance, it should be interpreted as a supplementary rather than a standalone prognostic marker.
Keywords: COVID-19; De Ritis ratio; ICU mortality
1. Introduction
Multiorgan involvement is a defining pathophysiological feature of severe coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The predilection of SARS-CoV-2 for extrapulmonary tissues is largely attributable to the ubiquitous expression of angiotensin-converting enzyme 2 (ACE2)—its principal cellular receptor—across anatomically diverse sites including the myocardium, hepatic parenchyma, renal tubules, intestinal epithelium, and vascular endothelium1,2, conferring a systemic vulnerability that fundamentally distinguishes COVID-19 from classical respiratory viral syndromes.
A dysregulated and self-amplifying cytokine cascade, compounded by endothelial activation and coagulopathy, precipitates organ failure at sites remote from the primary pulmonary focus3. Hepatic involvement ranks among the most frequently encountered extrapulmonary complications, with abnormal liver enzyme concentrations documented in 14–53% of hospitalised patients4. The pathogenesis of this hepatic derangement is multifactorial, encompassing direct viral cytopathic effects on hepatocytes, cytokine storm-mediated hepatitis, hypoxia-driven ischaemia–reperfusion injury, and pharmacological hepatotoxicity5.
Conventional hepatic monitoring focuses on absolute alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values, yet the ratio of AST to ALT—the De Ritis ratio—carries prognostic information that neither enzyme alone conveys. First described in 1957 as a tool for viral hepatitis classification6, the De Ritis ratio has subsequently been validated as a mortality-associated biomarker across a spectrum of critical conditions including sepsis, acute respiratory distress syndrome (ARDS), and cardiovascular disease7,8. Accumulating evidence from COVID-19 cohorts indicates that an elevated De Ritis ratio at the time of initial presentation correlates with heightened disease severity, escalating therapeutic demands, and reduced likelihood of survival9. Its derivability from universally available routine laboratory data, without imposing any additional diagnostic burden, renders it a highly practicable candidate for early prognostic stratification10. Against this background, the present investigation sought to determine whether the De Ritis ratio at ICU admission constitutes an independent prognostic determinant of mortality in critically ill patients with confirmed COVID-19.
2. Materials and Methods
We performed a retrospective cohort analysis at a single tertiary-care center. Medical records of 642 adults aged 18 years or above admitted to the Internal Medicine ICU of Sakarya University Training and Research Hospital between January and December 2021 were reviewed. Entry into the study required both RT-PCR–confirmed SARS-CoV-2 infection and a complete set of clinical and biochemical data available at ICU admission. Exclusion criteria included age below 18 years, unavailable clinical or laboratory records, death preceding formal ICU admission or occurring within the initial 24-hour period of ICU stay, and concurrent terminal malignancy or pregnancy.
Demographic data, chronic comorbid conditions, laboratory and hematological results at ICU admission, ventilatory support requirements, vasopressor and inotropic therapy, and definitive ICU outcome were extracted. Acute illness severity was quantified using the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scoring systems. The De Ritis ratio was defined as the quotient of AST to ALT at ICU admission. Patients were allocated to survivor or non-survivor subgroups based on ICU outcome.
2.1. Statistical Analysis
Baseline characteristics were summarised using standard descriptive measures. Continuous variables satisfying the normality assumption were characterised as mean ± SD; all others as median (IQR). Normally distributed variables were compared using the independent-samples t-test; the Mann–Whitney U test served as the non-parametric counterpart. Categorical variables were compared by chi-square testing. Independent determinants of ICU mortality were identified through two multivariable logistic regression models: Model A combined the APACHE II score with the De Ritis ratio, while Model B substituted the SOFA score. Calibration was checked with the Hosmer–Lemeshow test; discriminatory capacity was evaluated by ROC curves and AUC values. Two-tailed p values below 0.05 were considered statistically significant. All computations were carried out using IBM SPSS Statistics, version 22.0.
The study protocol was approved by the Clinical Research Ethics Committee of Sakarya University Faculty of Medicine (Approval Date: March 25, 2023; Decision No: 115). The study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Due to the retrospective design and use of anonymised patient data, the requirement for written informed consent was waived.
3. Results
A total of 642 COVID-19 patients admitted to the Internal Medicine ICU were eligible for analysis. ICU survival was achieved by 301 patients (46.9%); the remaining 341 (53.1%) died. Mean age was 69.50 ± 14.18 years. Non-survivors were modestly older (70.82 ± 14.34 vs. 68.01 ± 13.86 years; p = 0.012). Sex distribution was identical in both groups. Demographic and comorbidity data are given in Table 1.
Table 1. Baseline demographic characteristics and comorbidities at ICU admission
| Variable | Survivors (n=301) | Non-survivors (n=341) | Total (N=642) | p |
|---|---|---|---|---|
| Age (years) | 68.01±13.86 | 70.82±14.34 | 69.50±14.18 | 0.012 |
| Female sex, n (%) | 136 (45.2) | 154 (45.2) | 290 (45.2) | 0.995 |
| Malignancy, n (%) | 18 (6.0) | 52 (15.3) | 70 (10.9) | <0.001 |
| DM, n (%) | 104 (34.6) | 107 (31.4) | 211 (32.9) | 0.393 |
| HT, n (%) | 156 (51.8) | 187 (54.8) | 343 (52.0) | 0.445 |
| Coronary artery disease, n (%) | 70 (23.3) | 98 (28.7) | 168 (26.2) | 0.115 |
| Heart failure, n (%) | 29 (9.6) | 42 (12.3) | 71 (11.1) | 0.280 |
| COPD, n (%) | 21 (7.0) | 35 (10.3) | 56 (8.7) | 0.140 |
| Asthma, n (%) | 11 (3.7) | 15 (4.4) | 26 (4.0) | 0.633 |
| CKD, n (%) | 27 (9.0) | 41 (12.0) | 68 (10.6) | 0.209 |
Data are presented as mean ± SD or n (%). DM: diabetes mellitus; HT: hypertension; COPD: chronic obstructive pulmonary disease; CKD: chronic kidney disease.
Malignancy was markedly more prevalent among non-survivors (15.3% vs. 6.0%; p < 0.001; OR: 2.83; 95% CI: 1.62–4.96). Vasopressor therapy was required far more frequently among non-survivors (59.2% vs. 29.9%; OR: 3.41; 95% CI: 2.43–4.78; p < 0.001), as was invasive mechanical ventilation (72.4% vs. 21.9%; OR: 9.35; 95% CI: 6.50–13.45; p < 0.001). Results for all pharmacological and mechanical support interventions are detailed in Table 2.
Table 2. Association between pharmacological and mechanical support interventions and ICU mortality
| Clinical Intervention | Survivors (n=301) | Non-survivors (n=341) | Total (N=642) | OR (95% CI) | p |
|---|---|---|---|---|---|
| Vasopressor use, n (%) | 90 (29.9) | 202 (59.2) | 292 (45.5) | 3.41 (2.43–4.78) | <0.001 |
| Inotropic support, n (%) | 41 (13.6) | 76 (22.3) | 117 (18.2) | 1.83 (1.22–2.76) | 0.004 |
| Invasive mechanical ventilation, n (%) | 66 (21.9) | 247 (72.4) | 313 (48.8) | 9.35 (6.50–13.45) | <0.001 |
| Non-invasive ventilation, n (%) | 52 (17.3) | 117 (34.3) | 169 (26.3) | 2.49 (1.71–3.62) | <0.001 |
| High-flow nasal oxygen, n (%) | 45 (15.0) | 96 (28.2) | 141 (22.0) | 2.23 (1.48–3.36) | <0.001 |
Data are presented as n (%). ORs calculated using univariate logistic regression. OR: odds ratio; CI: confidence interval.
Routine blood count indices showed no statistically significant variation between outcome groups. Inflammatory markers diverged sharply: IL-6, CRP, and ferritin were each significantly higher in patients who died (p = 0.006, p = 0.002, and p = 0.023). Absolute AST and ALT values were comparable between outcome groups (AST: p = 0.177; ALT: p = 0.497). The De Ritis ratio was significantly higher in non-survivors (1.82 ± 0.99 vs. 1.60 ± 0.86; p = 0.003). Full laboratory results are in Table 3.
Table 3. Comparison of laboratory parameters at ICU admission between survivors and non-survivors
| Parameter | Survivors (n=301) | Non-survivors (n=341) | Total (N=642) | p |
|---|---|---|---|---|
| Leukocyte (×10³/μL) | 10.70±11.42 | 11.25±7.34 | 10.99±9.48 | 0.469 |
| Lymphocyte (×10³/μL) | 0.84±0.93 | 1.03±2.05 | 0.94±1.63 | 0.121 |
| Neutrophil (×10³/μL) | 9.16±10.00 | 9.64±6.61 | 9.41±8.37 | 0.470 |
| Hemoglobin (g/dL) | 12.00±2.11 | 11.93±2.14 | 11.97±2.13 | 0.661 |
| Platelet (×10³/μL) | 235.54±105.00 | 222.11±103.70 | 228.41±104.44 | 0.104 |
| D-dimer (ng/mL) | 731 (503–1840) | 1050 (559–2215) | 890 (540–2030) | 0.003 |
| Ferritin (ng/mL) | 641 (279–1474) | 900 (432–2000) | 770 (350–1800) | 0.023 |
| IL-6 (pg/mL) | 38 (19–96) | 58 (24–141) | 48 (21–118) | 0.006 |
| CRP (mg/L) | 93 (54–154) | 110 (64–180) | 101 (58–170) | 0.002 |
| LDH (U/L) | 456 (331–590) | 485 (376–625) | 470 (350–610) | 0.058 |
| Urea (mg/dL) | 57 (42–88) | 67 (45–100) | 62 (44–94) | 0.006 |
| Creatinine (mg/dL) | 1.27±1.36 | 1.47±1.35 | 1.37±1.35 | 0.063 |
| Albumin (g/L) | 30.03±4.55 | 29.08±5.13 | 29.52±4.89 | 0.011 |
| Globulin (g/L) | 22.77±12.84 | 24.09±14.13 | 23.47±13.55 | 0.219 |
| CK-MB (U/L) | 27.10±18.83 | 31.84±30.67 | 29.63±25.92 | 0.022 |
| AST (U/L) | 37 (26–55) | 39 (26–61) | 38 (26–58) | 0.177 |
| ALT (U/L) | 26 (15–47) | 25 (15–44) | 25 (15–45) | 0.497 |
| De Ritis ratio | 1.60±0.86 | 1.82±0.99 | 1.72±0.94 | 0.003 |
Data are presented as mean ± SD or median (IQR). IL-6: interleukin-6; CRP: C-reactive protein; LDH: lactate dehydrogenase; CK-MB: creatine kinase–myocardial band; AST: aspartate aminotransferase; ALT: alanine aminotransferase.
Severity score values were substantially higher among non-survivors: APACHE II 19.07 ± 7.37 vs. 15.60 ± 7.06 (p < 0.001), and SOFA 6.80 ± 2.72 vs. 5.35 ± 2.55 (p < 0.001) (Table 4).
Table 4. Comparison of prognostic scoring systems between survivors and non-survivors
| Parameter | Survivors (n=301) | Non-survivors (n=341) | Total (N=642) | p |
|---|---|---|---|---|
| APACHE II score | 15.60±7.06 | 19.07±7.37 | 17.44±7.43 | <0.001 |
| SOFA score | 5.35±2.55 | 6.80±2.72 | 6.12±2.74 | <0.001 |
| De Ritis ratio | 1.60±0.86 | 1.82±0.99 | 1.72±0.94 | 0.003 |
Data are presented as mean ± SD. APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment.
Multivariable logistic regression established the De Ritis ratio as an independent predictor of ICU mortality across both models. In Model A, APACHE II (OR: 1.07; 95% CI: 1.05–1.09; p < 0.001) and De Ritis ratio (OR: 1.27; 95% CI: 1.06–1.51; p = 0.009) each retained significance. Model B yielded analogous findings for SOFA (OR: 1.23; 95% CI: 1.16–1.30; p < 0.001) and De Ritis ratio (OR: 1.26; 95% CI: 1.05–1.50; p = 0.013) (Table 5).
Table 5. Multivariable logistic regression analysis for ICU mortality
| Model | Variable | OR (95% CI) | p |
|---|---|---|---|
| Model A | APACHE II score | 1.07 (1.05–1.09) | <0.001 |
| De Ritis ratio | 1.27 (1.06–1.51) | 0.009 | |
| Model B | SOFA score | 1.23 (1.16–1.30) | <0.001 |
| De Ritis ratio | 1.26 (1.05–1.50) | 0.013 |
OR: odds ratio; CI: confidence interval.
Standalone ROC analysis demonstrated modest but significant discrimination for the De Ritis ratio (AUC: 0.562; 95% CI: 0.517–0.606; p = 0.007). When incorporated into composite models, performance improved: AUC 0.652 (95% CI: 0.609–0.694) for the APACHE II–based model and 0.661 (95% CI: 0.619–0.703) for the SOFA-based model (Table 6, Figure 1).
Table 6. ROC curve analysis
| Model | AUC | 95% CI | p |
|---|---|---|---|
| De Ritis ratio | 0.562 | 0.517–0.606 | 0.007 |
| APACHE II score + De Ritis ratio | 0.652 | 0.609–0.694 | <0.001 |
| SOFA score + De Ritis ratio | 0.661 | 0.619–0.703 | <0.001 |
AUC: area under the curve; CI: confidence interval.
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Cite this article
Hüseyin Özkök, Şeyma Şenocak, Özlem Aktürk, Ahmed Cihad Genç, Deniz Çekiç, Yusuf Durmaz, Ahmed Bilal Genç, Selçuk Yaylacı. The Role of the De Ritis Ratio in ICU Mortality Among Critically Ill Patients with COVID-19. Journal of Cukurova Anesthesia and Surgical Sciences. 9(2):427-434. https://doi.org/10.36516/jocass.1903636