Effect of Severe Fever With Thrombocytopenia Syndrome Virus Genotype on Disease Severity, Viral Load, and Cytokines in South Korea

Abstract

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by Bandavirus dabieense (SFTS virus [SFTSV]). Recently, at least 6 different genotypes of SFTSV have been identified, with genotypes A, D, and F dominant in China and B dominant in Japan and Korea. This study investigated the effect of SFTSV genotypes circulating in South Korea on disease severity, viral load, and cytokine profile.

Methods: We prospectively enrolled 70 patients with SFTS from July 2015 to June 2022. Serial plasma samples were obtained during hospitalization and analyzed. Viral load was measured by real-time reverse-transcription polymerase chain reaction. Partial sequences of the viral genome were analyzed for genotyping. Plasma concentrations of 17 cytokines were measured by multiplex-bead immunoassay.

Results: Of 70 samples, 51 could be genotyped. Genotype B was predominant (80.4%) and other genotypes were uncommon. Intensive care unit admission rates (51.2% vs 50.0%) and mortality rates (26.8% vs 40.0%) did not show any significant differences between genotype B and non-B genotypes. The initial viral load did not show any significant differences (3.59 vs 3.64 log copies/μL), whereas viral load measured at hospital day 3-4 tended to be higher in genotype B than non-B genotypes (3.83 vs 1.83 log copies/μL, P = .07). Additionally, the plasma concentrations of interferon-α, interleukin 10, and interferon-γ-induced protein 10, which are closely related to mortality in cases of SFTS, did not show any significant differences.

Conclusions: SFTSV genotype B was the prevalent genotype in South Korea, with no genotype-specific difference in clinical outcomes, initial viral load, or cytokine profiles.

Keywords: SFTS; cytokines; genotype; severe fever with thrombocytopenia syndrome; viral load.

Figure 1.

Viral load kinetics of patients infected with severe fever with thrombocytopenia syndrome virus genotype B and non-B genotypes. The values of each group were compared by Mann-Whitney U test. Abbreviation: N/A, not available.

Figure 2.

Detailed cytokine kinetics of patients infected with severe fever with thrombocytopenia syndrome virus genotype B and non-B genotypes. The values of each group were compared by Mann-Whitney U test. In the period between hospital day 7 and 10, the sample size was insufficient for analysis; therefore, the results are expressed as not available. Abbreviations: G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN-α, interferon alpha; IFN-γ, interferon gamma; IL, interleukin; IP-10, interferon gamma–induced protein 10; MCP-1, monocyte chemotactic protein 1; MIP-1α, macrophage inflammatory protein 1α; N/A, not available; RANTES, regulated on activation and normally T-cell expressed and secreted; TNF-α, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor.

Figure 3.

Viral load kinetics of survivors and nonsurvivors infected with severe fever with thrombocytopenia syndrome virus genotype B. The values of each group were compared by Mann-Whitney U test. Abbreviation: N/A, not available.

Figure 4.

Detailed cytokine kinetics of survivors and nonsurvivors infected with severe fever with thrombocytopenia syndrome virus genotype B. The values of each group were compared by Mann-Whitney U test. Abbreviations: G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN-α, interferon alpha; IFN-γ, interferon gamma; IL, interleukin; IP-10, interferon gamma–induced protein 10; MCP-1, monocyte chemotactic protein 1; MIP-1α, macrophage inflammatory protein 1α; N/A, not available; RANTES, regulated on activation and normally T-cell expressed and secreted; TNF-α, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor.