Reactivation of Epstein-Barr virus in SFTSV infected patients

Abstract

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus SFTSV with case fatality up to 30%. The reactivation of Epstein-Barr virus (EBV) has been proven to occur in individuals with various immune suppression conditions.

Methods: Here, we diagnosed 22 SFTSV infected patients with PCR in a hospital in Shandong Province, China in 2020. To understand the consequences of SFTSV infection leading to EBV reactivation, we examined EBV reactivation in SFTSV-infected patients with PCR and RT-PCR.

Results: We found that EBV was reactivated in 18.2% (4/22) of SFTS patients, suggesting that EBV reactivation is common in SFTS patients. Compared with SFTS patients without EBV reactivation, SFTS patients with EBV-reactivation had a significantly lower median level of serum albumin (32.45 g/L vs. 26.95 g/L, p = 0.03) and a significantly higher median number of urine red blood cells (0 cells/μL vs. 9 cells/μL, p = 0.04).

Conclusion: SFTS infection can reactivate EBV in patients, which may make the clinical condition of patients worsen.

Keywords: Epstein-Barr virus; Glomerular injury; Reactivation; Severe fever with thrombocytopenia syndrome virus.

Fig. 1

Reactivation of EBV in the SFTS patients. (A) 2 blood samples in the Non-EBV group were insufficient for analysis, thus the total sample numbers of the non-EBV group and EBV group were 16 and 4, respectively. The median level of EBV IgG was 25.02 ng/mL and 25.14 ng/mL, respectively and the difference between the 2 groups was analyzed with the Mann-Whitney test (p = 0.60). The total sample number of the non-EBV group and EBV group were 18 and 4, respectively and the difference between the 2 groups on EVI2 was analyzed with the Mann-Whitney test (p = 0.06) in (B) Ns indicated there was no significant difference between the 2 groups. A red line in Figure 1B indicated value 1.

Fig. 2

The level of plasma albumin and microscopic examination of urine red blood cell count. (A) The total sample number of EBV-negative and EBV-positive SFTS patients was 18 and 4, respectively and the difference between the 2 groups was performed with the Mann-Whitney test (p = 0.03). (B) The total sample number of EBV-negative and EBV-positive SFTS patients was 14 and 3, respectively and the difference between the 2 groups was performed with the Mann-Whitney test (p = 0.04).

Fig. 3

Phylogenetic analysis of SFTSV sequences from patients from Qingdao City and adjacent areas, Shandong Province, China from April to September 2020. The tree was generated using the Maximum Likelihood method, the Kimura 2-parameter model and 1,000 replicates for bootstrap testing in MEGA 7.0 software. Only bootstrap values > 50% were shown. Each SFTSV strain from this study was shown with a dot. Scale bar indicated nucleotide substitutions per site. The SFTSV strains from this study were numbered from 1 to 18 and the GenBank accession numbers of reference sequences were shown in each line.