Clinical manifestations of death with severe fever and thrombocytopenia syndrome: A meta‐analysis and systematic review

Wang, Xiankun; Ren, Xiaotun; Ge, Ziruo; Cui, Shu; Wang, Lin; Chen, Zhihai; Tian, Di

doi:10.1002/jmv.26518

Cited by 21 publications

(10 citation statements)

References 34 publications

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“…The results of routine blood tests failed in consistency intensively according to previous published papers [ 6 , 7 , 9 ]. This discrepancy can be primarily attributed to the differences of sample sizes and study regions.…”

Section: Discussionmentioning

confidence: 84%

“…Liu MM et al found that old age, central nervous system manifestations, bleeding tendency, elevated serum enzymes and high vial load were risk factors for fatality among SFTS patients [ 6 ]. Wang X et al found that there were some significant differences between the nonfatal and fatal groups, such as headache, fatigue, diarrhea, vomiting and arrhythmia [ 7 ]. Dualis et al emphasized the importance of delay in hospital admission, high viral load, older age and presence of comorbid or complications on risk of dying of SFTS cases [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Clinical laboratory parameters and fatality of Severe fever with thrombocytopenia syndrome patients: A systematic review and meta-analysis

et al. 2022

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Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high case fatality rate. Unfortunately, no vaccine or antiviral specifically targeting SFTS virus (SFTSV) are available for the time being. Our objective was to investigate the association between clinical laboratory parameters and fatality of SFTS patients. Methods The systematic review was conducted in accordance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We searched (from inception to 24th February 2022) Web of Science, PubMed, National Knowledge Infrastructure databases and Wan Fang Data for relevant researchers on SFTS. Studies were eligible if they reported on laboratory parameters of SFTS patients and were stratified by clinical outcomes. A modified version of Newcastle-Ottawa scale was used to evaluate the quality of included studies. Standardized mean difference (SMD) was used to evaluate the association between laboratory parameters and outcomes. The between-study heterogeneity was evaluated quantitatively by standard Chi-square and the index of heterogeneity (I2). Heterogeneity was explored by subgroup and sensitivity analyses, and univariable meta-regression. Publication bias was determined using funnel plots and Egger’s test. Results We identified 34 relevant studies, with over 3300 participants across three countries. The following factors were strongly (SMD>1 or SMD<-0.5) and significantly (P<0.05) associated mortality: thrombin time (TT) (SMD = 1.53), viral load (SMD = 1.47), activated partial-thromboplastin time (APTT) (SMD = 1.37), aspartate aminotransferase (AST) (SMD = 1.19), lactate dehydrogenase (LDH) (SMD = 1.13), platelet count (PLT) (SMD = -0.47), monocyte percentage (MON%) (SMD = -0.47), lymphocyte percentage (LYM%) (SMD = -0.46) and albumin (ALB) (SMD = -0.43). Alanine aminotransferase, AST, creatin phosphokinase, LDH, PLT, partial-thromboplastin time and viral load contributed to the risk of dying of SFTS patients in each subgroup analyses. Sensitivity analysis demonstrated that the results above were robust. Conclusions/significance The abnormal levels of viral load, PLT, coagulation function and liver function, significantly increase the risk of SFTS mortality, suggesting that SFTS patients with above symptoms call for special concern.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Clinical laboratory parameters and fatality of Severe fever with thrombocytopenia syndrome patients: A systematic review and meta-analysis

et al. 2022

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“…On the other hand, the association between male and adverse outcomes, including mortality, do not consistently exhibit, which differed across studies (Jung et al, 2019;Wang et al, 2020). More intriguingly, the risk factors that are known to change with sex and age are often interacted, which likely explain the sex differences observed for the mortality risk.…”

Section: Introductionmentioning

confidence: 93%

Sex Differences in Case Fatality Rate of Patients With Severe Fever With Thrombocytopenia Syndrome

Zhao

et al. 2021

Front. Microbiol.

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Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne disease with high mortality. However, detailed analysis is lacking to explore the complex effect of sex with age or comorbidities.Methods: A retrospective cohort study was performed among 2,938 SFTS patients entered during 2011–2020 in Xinyang, China. The case fatality rate (CFR) was estimated for their association with sex, age, and comorbidities by an interactive way. The difference of immune response between sex was explored in an age dependent way.Results: An overall CFR of 15.3% (450/2,938) was obtained, which appeared to be higher in males than in females [17.7% vs. 13.6%, adjusted odds ratio (aOR) = 1.24; 95% CI, 1.00–1.53; P = 0.048] and increased dramatically with age (P < 0.001). The associations between sex and SFTS fatal outcome were age-dependent and varied according to the status of comorbidities. The mortality-related risk conferred by older age was more pronounced in males, with aOR (95% CI) to be 5.76 (3.75–8.84) vs. 5.30 (3.54–7.95) in female. Sex-stratified analysis disclosed significant associations between death and comorbidities among female patients (aOR = 1.87, 95% CI: 1.40–2.49; P < 0.001), while none among males. Among females, the significant associations between presence of comorbidity and fatal outcome differed among age groups, with aOR (95% CI) decreased from 2.28 (1.16–4.46) in ≤60 years, to 2.06 (1.34–3.18) in 60–70 years and further to 1.55 (0.97–2.47) in >70 years. Altogether 194 SFTS patients were randomly selected for the test of B cells, natural killer (NK) cells, CD4 cells percentages, and anti-SFTSV IgM antibody level, the results revealed that males >60 years had significantly decreased percentages of B cells, CD4 cells, lower anti-SFTSV IgM antibody titer, and increased level of NK cells than male aged ≤60 years, while none of these age specific differences was observed in the females. This finding underlies the more pronounced age specific difference in CFR among male than female.Conclusions: Males had a significantly higher mortality of SFTS than did females, and more likely to be affected by aging for SFTS mortality. This difference can be explained by the effect from comorbidities and the host immunity. It is essential to take a sex- and age-based approach to SFTS treatment and management.

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“…It is currently unclear whether neurons can be infected by SFTSV or viruses harboring SFTSV glycoproteins. Neurologic symptoms have been observed in human SFTS cases, but it remains unclear whether the SFTSV glycoproteins can initiate entry into neurons in vivo (52). To test the neuropathogenic potential of rVSV-SFTSV, we injected escalating doses of rVSV-SFTSV or VSV Indiana strain intracranially into the right cerebral hemisphere of 4-weekold C57BL/6 mice and observed the mice for 14 days.…”

Section: Rvsv-sftsv Is Attenuated In Ifnar -/Mice and Exhibits A Favorable Safety Profilementioning

confidence: 99%

Safety, Immunogenicity and Efficacy of a Recombinant Vesicular Stomatitis Virus Vectored Vaccine Against Severe Fever with Thrombocytopenia Syndrome Virus and Heartland Bandaviruses

Hicks

Westover

Manzoni³

et al. 2021

Preprint

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Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 8,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation and promiscuity in incorporating foreign glycoproteins into its virions. In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity and efficacy in mice. We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of Ifnar-/- mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection against lethal SFTSV challenge. Additionally, passive transfer of sera from immunized Ifnar-/- mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects mice against challenge with the closely related Heartland virus despite low neutralizing titers to the virus. Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate.ImportanceTick borne diseases are a growing threat to human health. Severe fever with thrombocytopenia syndrome (SFTS) and Heartland viruses are recently recognized, highly-pathogenic, tick-transmitted viruses. The fatality rates for individuals infected with SFTSV or HRTV are high and there are no therapeutics or vaccines available. The recent introduction of the tick vector for SFTSV (Haemaphysalis longicornis) to the eastern half of the United States and Austrailia raises concerns for SFTSV outbreaks outside East Asia. Here we report the development of a potential vaccine for SFTSV and HRTV based on the viral vector platform that has been successfully used for an Ebola vaccine. We demonstrate that the rVSV-SFTSV protects from lethal SFTSV or HRTV challenge when given as a single dose. We evaluated possible pathogenic effects of the vaccine and show that it is safe in immune compromised animlas and when introduced into the central nervous system.

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Clinical manifestations of death with severe fever and thrombocytopenia syndrome: A meta‐analysis and systematic review

Cited by 21 publications

References 34 publications

Clinical laboratory parameters and fatality of Severe fever with thrombocytopenia syndrome patients: A systematic review and meta-analysis

Clinical laboratory parameters and fatality of Severe fever with thrombocytopenia syndrome patients: A systematic review and meta-analysis

Sex Differences in Case Fatality Rate of Patients With Severe Fever With Thrombocytopenia Syndrome

Safety, Immunogenicity and Efficacy of a Recombinant Vesicular Stomatitis Virus Vectored Vaccine Against Severe Fever with Thrombocytopenia Syndrome Virus and Heartland Bandaviruses

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