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Adult patients RT-PCR- confirmed-COVID-19

(n=220)

Adult patients RT-PCR- confirmed-COVID-19

(n=97)

Patients excluded due to missing data

(n=19)

Patients excluded due to missing data

(n=5)

Patients excluded due incomplete follow-up resolution at the cut-

off date (n=8)

Patients excluded due incomplete follow-up resolution at the cut-

off date (n=9)

Included patients (n=193)

Training set (n=149)

Included patients (n=83)

Test set (n=44)

WAVE 1 WAVE 2

Supplementary Figure S1. Flowchart of the patient selection process. RT-PCR: reverse transcription-polymerase chain reaction.

(2)

Supplementary Figure S2. The six-parameter signature of critical/fatal COVID-19 predicts disease prognosis in the training and test groups during the first wave of infection. ROC-AUC analysis of the combinations of the six biomarkers included in the signature.

(3)

1 - Specificity

1.0 0.8

0.6 0.4

0.2 0.0

Sensitivity

1.0

0.8

0.6

0.4

0.2

0.0

ROC Curve

<

L r

AUC NLR = 0.730 AUC LDH = 0.671

AUC C-reactive protein = 0.608 AUC Urea = 0.595

AUC d-Dimer = 0.564 AUC IL-6 = 0.532

AUC All Biomarkers = 0.874 Reference Line

0 20 40

IL-6 d-Dimer Urea C-reactive protein LDH NLR

50 100 150 200

10.571 (1.503 - 74.323) (P = 0.018) 18.663 (1.959 - 177.847) (P = 0.011)

1.201 (0.211 - 6.836) (P = 0.836)

5.617 (0.805 - 39.194) (P = 0.082)

0.639 (0.122 - 3.355) (P = 0.597)

0.556 (0.108 - 2.869) (P = 0.556) Odds Ratio (95% CI)

A

B

Supplementary Figure S3. Multivariate logistic regression analysis of the six-biomarker model built with data from wave 1 on critical/fatal COVID-19 prognosis during the second wave of infection. (A) ROC curves, AUC analyses, and (B) odds ratio plots, 95% confidence interval (CI) and P-value of the biomarkers included in the six-biomarker signature.

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