Comorbidity and Its Impact on the Fatal Outcome of Patients With Severe Fever With Thrombocytopenia Syndrome

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne disease with high mortality. However, a disaggregated data has been lacking to explore the effect of demography on the mortality. 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 comorbidities stratified by age and sex. The immune response was explored for the age and sex differences. Findings: The associations between comorbidities and SFTS fatal outcome were age- and sex-dependent. The effect of comorbidity on death was reduced with age, until to non-significant effects among patients >70 years old. Sex-stratified analysis disclosed significant associations between death and comorbidities for females (OR: 1·87, 95% CI: 1·40-2·49, p <0·001), while no effect in males. Older males had significantly decreased levels of B-cell, CD4-cell, anti-SFTSV IgM antibody and selected cytokines/chemokines than younger males, while no age differences in females. Among all comorbidities, chronic viral hepatitis displayed the greatest effect on SFTS mortality both alone and combined with other comorbidities. Ganulocytic myeloid-derived suppressor cells were expanded to a higher level in HBV-SFTS patients. Interpretation: Males are more likely to be affected by aging for SFTS mortality, relating to inequities of comorbidities for their risk of death from both age and sex. It is essential to take a sex- and age-based approach to SFTS treatment and management. Funding Information: National Natural Science Foundation of China and China Mega-project for Infectious Diseases. Declaration of Interests: The authors have declared that no conflict of interests exist. Ethics Approval Statement: The study was conducted in accordance with guidelines approved by the Ethics Committees from the 154 hospital of the Chinese people’s liberation Army. All participants provided written or verbal informed consent. All the data were analyzed anonymously.