Prediction of severe illness due to COVID-19 based on an analysis of initial Fibrinogen to Albumin Ratio and Platelet count

Abstract

Concomitant coagulation disorder can occur in severe patients withCOVID-19, but in-depth studies are limited. This study aimed to describe the parameters of coagulation function of patients with COVID-19 and reveal the risk factors of developing severe disease. This study retrospectively analyzed 113patients with SARS-CoV-2 infection in Taizhou Public Health Center. Clinical characteristics and indexes of coagulation function were collected. A multivariate Cox analysis was performed to identify potential biomarkers for predicting disease progression. Based on the results of multivariate Cox analysis, a Nomogram was built and the predictive accuracy was evaluated through the calibration curve, decision curve, clinical impact curve, and Kaplan-Meier analysis. Sensitivity, specificity, predictive values were calculated to assess the clinical value. The data showed that Fibrinogen, FAR, and D-dimer were higher in the severe patients, while PLTcount, Alb were much lower. Multivariate Cox analysis revealed that FAR and PLT count were independent risk factors for disease progression. The optimal cutoff values for FAR and PLT count were 0.0883 and 135*10⁹/L, respectively. The C-index [0.712 (95% CI = 0.610-0.814)], decision curve, clinical impact curve showed that Nomogram could be used to predict the disease progression. In addition, the Kaplan-Meier analysis revealed that potential risk decreased in patients with FAR<0.0883 and PLT count>135*10⁹/L.The model showed a good negative predictive value [(0.9474 (95%CI = 0.845-0.986)].This study revealed that FAR and PLT count were independent risk factors for severe illness and the severity of COVID-19 might be excluded when FAR<0.0883 and PLT count>135*10⁹/L.

Keywords: COVID-19; Coagulation and Fibrinolysis; fibrinogen-to-Albumin Ratio (FAR); non-Severe Survival (NSS); platelet count (PLT); prediction.

Figure1.

Comparison of initial indexes of coagulation function between severe and non-severe patients. Fibrinogen, D-dimer and FAR were significantly higher in the severe group than in the Non-Severe group (4.23 g/L vs.3.07 g/L, 0.32 mg/L vs. 0.24 mg/L,0.10 vs.0.078,P = .002,0.001,0.009), while PLT count and Alb were much lower (166*10/L vs.199 *10/L, 38.3 g/L vs.40.6 g/L, P = .034,0.005). The box was used to show the median and inter quartiles range.

Figure 2.

Temporal changes in markers of coagulation function over time inpatients with severe COVID-19. Dynamic changes in PT and aPTT (A), Fibrinogen and Alb(B), D-dimer(C), PLT and FAR(D).Coagulation time such as PT, aPTT shorten over time and leveled off in about 11–15 days in the hospital. Fibrinogen and D-dimer showed similar volatility changes, therein, Fibrinogen was lowest on day 11–15 after on admission, the median value was 3.5, while D-dimer was the highest of 0.89.FAR was highest on day 11–15 after admission and decreased during hospitalization,whilePLTcount increased rapidly before the stage of severe illness, than decreased from day 15^th.All data were displayed by median and inter quartiles range.

Figure 3.

Prediction of severity degree of COVID-19 patients. Nomograms were conveyed using PLT and FAR to predict 10-day non-severe survivaland 20 day non-severe survival ofCOVID-19 patients (A). Decision curve (B) and Clinical impact curve (C) of the Nomogram for non-severe survival in the 2019-nCoV cohort, in which the predicted probability of survival was compared well with the actual survival and had superior standardized net benefit. Calibration plot for 10-day non-severe survival using Nomograms with FAR and PLT count are shown (D), the c-index = 0.712 (95% CI = 0.610–0.814).(E) Area under the ROC curve (AUC) of FAR, PLT and FAR-PLT combination was 0.730,0.637 and 0.754, P = .001,0.015,0.030, respectively. The optimal cutoff values for FAR and PLT count were 0.0883 and 135*10/L.(F) Kaplan–Meier plots were determined by using the cutoff values, Group A vs. Group B long-rank χ2 = 7.511 P = .006, GroupA vs. Group C long-rank χ2 = 20.944 P = .000, while Group B vs. Group C long-rank χ2 = 3.615 P = .056; Group A:PLT≧135*10/L andFAR≤0.0883, Group B:PLT<135*10/Lor.