Host cytokine storm is associated with disease severity of severe fever with thrombocytopenia syndrome.
BACKGROUND
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease in China, caused by SFTS virus (SFTSV). Severe SFTS patients can quickly proceed to multiorgan dysfunction and death; however, underlying pathogenic mechanisms remain unclear.


METHODS
Serum samples from 15 fatal and 44 nonfatal SFTS cases were subjected to multiplex-microbead immunoassays to detect a broad spectrum of cytokines. The viral load and virus-specific IgG titers were also tested by real-time PCR and ELISA, respectively.


RESULTS
Cytokines IL-1RA, IL-6, IL-10, G-CSF, IP-10, and MCP-1 were elevated in SFTS patients and produced at robust levels in fatal cases. In contrast, cytokines PDGF-BB and RANTES decreased in SFTS patients. These cytokines reverted to normal ranges during the convalescent phase of SFTSV infection. Cytokines IL-1β, IL-8, MIP-1α, and MIP-1β showed a unique pattern of elevation in fatal cases but not in nonfatal cases. However, these cytokines increased in the convalescent phase of nonfatal SFTS cases. Our regression analysis revealed that the serum viral load correlated with these cytokines. Moreover, levels of these cytokines correlated with various clinical parameters and virus-specific IgG titers.


CONCLUSIONS
The study demonstrates that SFTSV infection induces a cytokine storm with abnormally expressed cytokine profiles, which are associated with the disease severity.
National Institute for Viral Disease Control and Prevention, China Centers for Disease Control and Prevention (CDC), China.
Yulan
Y
Sun
Cong
C
Jin
Faxian
F
Zhan
Xianjun
X
Wang
Mifang
M
Liang
Quanfu
Q
Zhang
Shujun
S
Ding
Xuhua
X
Guan
Xixiang
X
Huo
Chuan
C
Li
Jing
J
Qu
Qin
Q
Wang
Shuo
S
Zhang
Yanping
Y
Zhang
Shiwen
S
Wang
Anqiang
A
Xu
Zhenqiang
Z
Bi
Dexin
D
Li
D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D002044:Bunyaviridae Infections / Q000097:blood* / Q000276:immunology* / Q000401:mortality; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood*; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D016856:Phlebovirus / Q000235:genetics / Q000276:immunology*; D019562:Viral Load
D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G