Concurrent Measurement of Dynamic Changes in Viral Load, Serum Enzymes, T Cell Subsets, and Cytokines in Patients with Severe Fever with Thrombocytopenia Syndrome

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection caused by a novel Bunyavirus. Analysis on the dynamic changes of clinical, laboratory, and immunological abnormalities associated with SFTS in a concurrent study is lacking. Thirty-three SFTS patients were admitted to Jiangsu People's Hospital, Nanjing, China, and diagnosis was made based on the clinical symptoms and positive viral RNA detected by RT-PCR. Four patients deceased and twenty-nine survived. Blood samples were collected every other day between Day 5 and Day 15 from the onset of fever. Samples from healthy volunteers were used as normal controls. Peak viral RNA load, serum enzymes, IL-6, and IL-10 were significantly higher in deceased patients compared to survivors. Viral load, serum enzymes, and cytokines declined in survivors within 2 weeks from onset of fever. CD69+ T cells were elevated early after infection while HLA-DR+ and CTLA4+ T cells were elevated during the recovery phase of those who survived. High level SFTSV viral load was concurrently observed with reduced PLT, elevated serum enzymes, elevated pro-inflammatory and anti-inflammatory cytokines, and activation of CD69+ T cells. The degree and pattern of changes in these parameters may indicate the clinical outcome in SFTSV-infected patients.

Circulating regulatory T cells in patients with severe fever with thrombocytopenia syndrome

“…Reports have shown that subpopulations of T cells were found to be changed at different phases of SFTSV-infected patients [16,19]. The present study revealed that CD4  CD25 Foxp3  cells were up-regulated in the circulating blood of patients with SFTS, and the percentage of CD4  CD25 Foxp3  cells negatively correlated with the leukocyte counts in patients with SFTS.…”

A Case of Severe Fever With Thrombocytopenia Syndrome Accompanied by Self-Limiting Severe Proteinuria That Inversely Correlated With the Platelet Count

“…Deceased patients had significantly higher viral loads than those of survivors when measured on days 7 -9 after the onset of fever, and viral loads gradually decreased during the recovery phase [9]. Since the microbiology laboratory of our hospital does not meet the facility criteria for dealing with the SFTS virus, we were unable to measure the viral load.…”

“…A recent study showed that there was no significant difference in the lowest PLT count during the first week between 32 survival and deceased cases of SFTS in South Korea [10]. Li et al also reported that the PLT counts between both cases were very similar [9]. On the other hand, a study in northeast China showed that the lowest PLT count on admission or throughout hospitalization was associated with the severity of SFTS [11].…”

“…Although thrombocytopenia is a key abnormal finding in SFTS, there have been conflicting findings on the relationship between the PLT count and disease severity [9]. A recent study showed that there was no significant difference in the lowest PLT count during the first week between 32 survival and deceased cases of SFTS in South Korea [10].…”

Severe Fever with Thrombocytopenia Syndrome

“…In convalescent stage, most of critical clinical parameters such as body temperature, hematologic values, and serum enzymes are normalized [1]. Immunologic analysis of SFTS patients revealed that elevation of CD 69+ T cells was evident in acute phase after onset of illness and that HLA-DR+ and CTLA4+ T cells were increased in the convalescent phase [17]. In addition, Deng et al[18] reported that concentrations of TNF-β, IL 6, IFN-γ, and IFN-γ-induced protein 10 were associated with disease severity.…”