Derivation and Validation of a Predictive Score for Disease Worsening Inpatients with COVID-19

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease. COVID-19 is associated with excessive inflammation, platelet activation, endothelial dysfunction, blood coagulation activation and fibrin formation. Current management of patients hospitalized in an intensive care unit (ICU) is based on supportive care and the mortality rate is high. Blood hypercoagulability -documented by increase in D-Dimers and decrease in antithrombin (AT) -is frequently encountered among COVID-19 patients.

Aim: Identification of patients with COVID-19 being at high risk for clinical deterioration is a challenging issue for an earlier adapted treatment and positive clinical outcome. we aimed to identify the most relevant clinical and haematological risk factors for worsening of COVID-19 in hospitalized patients by and constructing an accurate risk assessment tool, COMPASS-COVID-19.

Methods: Patients with confirmed COVID-19 (n=430) were divided in derivation (n=310) and validation (n=120) cohorts. They were stratified to those hospitalized at the conventional ward (C-group) and those with worsening disease (W-group) admitted in ICU. The study endpoint was disease worsening. All patients were routinely evaluated with full blood count, prothrombin time, fibrinogen, D-Dimers, antithrombin and protein C activity. Data from the first hospitalization day at the conventional ward or the ICU were analyzed. Cardiovascular risk factors and comorbidities were routinely registered.

Results: In the derivation cohort, compensated DIC was diagnosed in 8.2% of patients in the C-group and in 28.2% of patients in the W-group (p=0.001). Compared to the C-group, the patients in the W-group had significantly lower levels of AT, PC, platelets, lymphocyte, monocyte and red blood cell counts as well as, hemoglobin and hematocrit. They had significantly higher levels of fibrinogen, DDimers, white blood cells and neutrophils counts. No difference was noted in eosinophil and basophil counts. Hematological predictors for disease worsening: Increase of fibrinogen (OR= 9.50, 95% CI:2.23-40.54) and D-Dimer levels (OR=7.65, 95% CI:2.67-21.87), a platelet count lower than 100x109/L (OR=7.60, 95% CI:1.55-37.35) and a positive compensated DIC-ISTH score (OR=4.58, CI:2.09-10.07) were major determinants of disease worsening risk. Deficiency of AT activity (OR = 2.13, 95%CI: 1.18-3.85), PT prolongation (OR=2.43, 95% CI:1.15-5.13), leukocytosis (OR=1.86, 95%CI:1.04-3.33), lymphopenia with lymphocyte count lower than 1.5 G/L (OR=3.37, CI:1.58-7.21) were significant risk factors for worsening disease. The multivariate analysis retained obesity- BMI≥30, (OR=6.56, 95%CI: 2.98-14.46; p<0.001), male gender (OR=2.59, 95% CI:1.29-5.21; p=0.007), compensated DICISTH score ≥5 (OR=2.58, 95% CI:1.07-6.21; p=0.034), lymphocyte count <1 G/L (OR=2.21, 95% CI:1.17-4.19; p=0.015) and Hb<11 g/dL (OR=2.25, 95% CI: 1.13-4.48; p=0.021) as significant predictors of worsening disease . The score at 18 points cut-off value identified as high risk for disease worsening 90% of patients at the W-group and 38% of the patients at the C-group. The sensitivity and the specificity of the score were 94% and 58% respectively and the negative and positive predictive values were 96% and 45% respectively.

Conclusion: The COMPASS-COVID- 19 score derived from multivariate analysis and includes obesity, gender, hemoglobin, lymphocyte and the cDIC-ISTH score (including platelet count, prothrombin time, D-Dimers antithrombin and protein C levels). The score has a very good discriminating capacity to stratify patients at high and low risk for worsening disease, with AUC value at 0.77, sensitivity 81% and specificity 60%. Application of the COMPASS-COVID-19 score at the validation cohort showed 96% sensitivity. The COMPASS-COVID-19 score is an accurate clinical decision tool for an easy identification of COVID-19 patients being at high risk for disease