The Evaluation of Surrogate Laboratory Parameters for Predicting the Trend of Viral Loads in Patients with Severe Fever with Thrombocytopenia Syndrome: Cross-Correlation Analysis of Time Series

Abstract

Background: There is a correlation between the severe fever with thrombocytopenia syndrome (SFTS) viral load and disease severity; however, measurement of viral load is difficult in general laboratory and it takes time to obtain a viral load value. Here, the laboratory parameters for predicting the dynamic changes in SFTS viral load were identified. In addition, we tried to evaluate a specific time point for the early determination of clinical deterioration using dynamic change of laboratory parameters.

Materials and methods: This observational study included SFTS patients in Korea (2013 - 2020). Cross-correlation analysis at lagged values was used to determine the temporal correlation between the SFTS viral loads and time-series variables. Fifty-eight SFTS patients were included in the non-severe group (NSG) and 11 in the severe group (SG).

Results: In the cross-sectional analyses, 10 parameters -white blood cell, absolute neutrophil cell, lymphocyte, platelet, activated partial thromboplastin time (aPTT), C-reactive protein, aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK)- were assessed within 30 days from the onset of symptoms; they exhibited three different correlation patterns: (1) positive, (2) positive with a time lag, and (3) negative. A prediction score system was developed for predicting SFTS fatality based on age and six laboratory variables -platelet, aPTT, AST, ALT, LDH, and CPK- in 5 days after the onset of symptoms; this scoring system had 87.5% sensitivity and 86.0% specificity (95% confidence interval: 0.831 - 1.00, P <0.001).

Conclusion: Three types of correlation patterns between the dynamic changes in SFTS viral load and laboratory parameters were identified. The dynamic changes in the viral load could be predicted using the dynamic changes in these variables, which can be particularly helpful in clinical settings where viral load tests cannot be performed. Also, the proposed scoring system could provide timely treatment to critical patients by rapidly assessing their clinical course.

Keywords: Banyangvirus; Cross-correlation analysis; Fatality prediction; Severe fever with thrombocytopenia syndrome; Tick-borne disease.