Discriminant Models for the Prediction of Viral Shedding Time and Disease Progression in COVID-19

Background: COVID-19 infection can cause life-threatening respiratory disease. This study aimed to fully characterize the clinical features associated with postponed viral shedding and disease progression, then develop and validate two prognostic discriminant models. Methods This study included 125 hospitalized patients with COVID-19. 44 parameters were recorded, including age, gender, underlying comorbidities, epidemic features, laboratory indexes, imaging characteristics and therapeutic regimen, et al. F-test and χ 2 test were used for feature selection. All models were developed with 4-fold cross-validation, and the final performances of each model were compared by the Area Under Receiving Operating Curve (AUROC). After optimizing the parameters via L 2 regularization, prognostic discriminant models were built to predict postponed viral shedding and disease progression of COVID-19 infection. The test set was then used to detect the predictive values via assessing models sensitivity and specificity. Results 69 patients had a postponed viral shedding time (> 14 days), and 28 of 125 patients progressed into severe cases. Eleven and six demographic, clinical features and therapeutic regimen were significantly associated with postponed viral shedding and disease progressing, respectively ( p  < 0.05). The optimal discriminant models are: y 1 (postponed viral shedding) = -0.244 + 0.2829x 1 (the interval from the onset of symptoms to antiviral treatment) + 0.2306x 4 (age) + 0.234x 28 (Urea) − 0.2847x 34 (Dual-antiviral therapy) + 0.3084x 38 (Treatment with antibiotics) + 0.3025x 21 (Treatment with Methylprednisolone); y 2 (disease progression) = -0.348–0.099x 2 (interval from Jan 1st, 2020 to individualized onset of symptoms) + 0.0945x 4 (age) + 0.1176x 5 (imaging characteristics) + 0.0398x 8 (short- term exposure to Wuhan) − 0.1646x 19 (lymphocyte counts) + 0.0914x 20 (neutrophil counts) + 0.1254x 21 (neutrphil/lymphocyte ratio) + 0.1397x 22 (C-Reactive Protein) + 0.0814x 23 (Procalcitonin) + 0.1294x 24 (Lactic dehydrogenase) + 0.1099x 29 (Creatine kinase). The output ≥ 0 predicted postponed viral shedding or disease progressing to severe/critical state. These two models yielded the maximum AUROC, and faired best in terms of prognostic performance (sensitivity of 73.3%, 75%, and specificity of 78.6%, 75% for prediction of postponed viral shedding and disease severity, respectively). Conclusion The two discriminant models could effectively predict the postponed viral shedding and disease severity, and be used as early-warning tools for COVID-19.