Background: The severity of COVID-19 associates with the clinical decision making and the prognosis of COVID-19 patients, therefore, early identification of patients who are likely to develop severe or critical COVID-19 is critical in clinical practice. The aim of this study was to screen severity-associated markers and construct an assessment model for predicting the severity of COVID-19.
Methods: 172 confirmed COVID-19 patients were enrolled from two designated hospitals in Hangzhou, China. Ordinal logistic regression was used to screen severity-associated markers. Least Absolute Shrinkage and Selection Operator (LASSO) regression was performed for further feature selection. Assessment models were constructed using logistic regression, ridge regression, support vector machine and random forest. The area under the receiver operator characteristic curve (AUROC) was used to evaluate the performance of different models. Internal validation was performed by using bootstrap with 500 re-sampling in the training set, and external validation was performed in the validation set for the four models, respectively.
Results: Age, comorbidity, fever, and 18 laboratory markers were associated with the severity of COVID-19 (all P values <0.05). By LASSO regression, eight markers were included for the assessment model construction. The ridge regression model had the best performance with AUROCs of 0.930 (95% CI, 0.914-0.943) and 0.827 (95% CI, 0.716-0.921) in the internal and external validations, respectively. A risk score, established based on the ridge regression model, had good discrimination in all patients with an AUROC of 0.897 (95% CI 0.845-0.940), and a well-fitted calibration curve. Using the optimal cutoff value of 71, the sensitivity and specificity were 87.1% and 78.1%, respectively. A web-based assessment system was developed based on the risk score.
Conclusions: Eight clinical markers of lactate dehydrogenase, C-reactive protein, albumin, comorbidity, electrolyte disturbance, coagulation function, eosinophil and lymphocyte counts were associated with the severity of COVID-19. An assessment model constructed with these eight markers would help the clinician to evaluate the likelihood of developing severity of COVID-19 at admission and early take measures on clinical treatment.

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This is a list of supplementary files associated with this preprint. Click to download.
Additional file 1: Table S1. Associations of continuous laboratory markers with the severity of COVID-19 in the training set. Table S2. Remaining frequency of the 16 markers in 1,000 LASSO regression models. Table S3. Associations of the selected eight markers with the severity of COVID-19 in the external validation set (DOCX).
Additional file 1: Table S1. Associations of continuous laboratory markers with the severity of COVID-19 in the training set. Table S2. Remaining frequency of the 16 markers in 1,000 LASSO regression models. Table S3. Associations of the selected eight markers with the severity of COVID-19 in the external validation set (DOCX).
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Posted 16 Dec, 2020
On 02 Dec, 2020
On 02 Dec, 2020
On 02 Dec, 2020
Received 21 Nov, 2020
On 21 Nov, 2020
On 29 Oct, 2020
Received 10 Oct, 2020
On 30 Aug, 2020
Invitations sent on 27 Aug, 2020
On 24 Aug, 2020
On 23 Aug, 2020
On 23 Aug, 2020
On 22 Jul, 2020
Posted 16 Dec, 2020
On 02 Dec, 2020
On 02 Dec, 2020
On 02 Dec, 2020
Received 21 Nov, 2020
On 21 Nov, 2020
On 29 Oct, 2020
Received 10 Oct, 2020
On 30 Aug, 2020
Invitations sent on 27 Aug, 2020
On 24 Aug, 2020
On 23 Aug, 2020
On 23 Aug, 2020
On 22 Jul, 2020
Background: The severity of COVID-19 associates with the clinical decision making and the prognosis of COVID-19 patients, therefore, early identification of patients who are likely to develop severe or critical COVID-19 is critical in clinical practice. The aim of this study was to screen severity-associated markers and construct an assessment model for predicting the severity of COVID-19.
Methods: 172 confirmed COVID-19 patients were enrolled from two designated hospitals in Hangzhou, China. Ordinal logistic regression was used to screen severity-associated markers. Least Absolute Shrinkage and Selection Operator (LASSO) regression was performed for further feature selection. Assessment models were constructed using logistic regression, ridge regression, support vector machine and random forest. The area under the receiver operator characteristic curve (AUROC) was used to evaluate the performance of different models. Internal validation was performed by using bootstrap with 500 re-sampling in the training set, and external validation was performed in the validation set for the four models, respectively.
Results: Age, comorbidity, fever, and 18 laboratory markers were associated with the severity of COVID-19 (all P values <0.05). By LASSO regression, eight markers were included for the assessment model construction. The ridge regression model had the best performance with AUROCs of 0.930 (95% CI, 0.914-0.943) and 0.827 (95% CI, 0.716-0.921) in the internal and external validations, respectively. A risk score, established based on the ridge regression model, had good discrimination in all patients with an AUROC of 0.897 (95% CI 0.845-0.940), and a well-fitted calibration curve. Using the optimal cutoff value of 71, the sensitivity and specificity were 87.1% and 78.1%, respectively. A web-based assessment system was developed based on the risk score.
Conclusions: Eight clinical markers of lactate dehydrogenase, C-reactive protein, albumin, comorbidity, electrolyte disturbance, coagulation function, eosinophil and lymphocyte counts were associated with the severity of COVID-19. An assessment model constructed with these eight markers would help the clinician to evaluate the likelihood of developing severity of COVID-19 at admission and early take measures on clinical treatment.

Figure 1

Figure 2

Figure 2

Figure 3

Figure 3

Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
Additional file 1: Table S1. Associations of continuous laboratory markers with the severity of COVID-19 in the training set. Table S2. Remaining frequency of the 16 markers in 1,000 LASSO regression models. Table S3. Associations of the selected eight markers with the severity of COVID-19 in the external validation set (DOCX).
Additional file 1: Table S1. Associations of continuous laboratory markers with the severity of COVID-19 in the training set. Table S2. Remaining frequency of the 16 markers in 1,000 LASSO regression models. Table S3. Associations of the selected eight markers with the severity of COVID-19 in the external validation set (DOCX).
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