Long-term clinical sequelae in severe fever with thrombocytopenia syndrome: A longitudinal cohort study

Abstract

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease characterized by a high case fatality rate. Despite extensive research on acute-phase manifestations, the long-term clinical sequelae in survivors remain poorly characterized. Methods In this prospective cohort study from 2010 to 2024, 1,197 SFTS survivors and 188 age/sex-matched febrile controls without SFTS were enrolled from the highest endemic region in China. Participants underwent face-to-face interview, serial clinical evaluations and laboratory testing at 6, 12, 18 and 24 months post-discharge, with extended follow-up for a subset (n=294) over 11 years. Propensity score matching and multivariate logistic regression were used to determine the factors associated with long-term sequelae risk. Results A total of 62.57% (749/1,197) of survivors developed persistent sequelae, significantly higher than controls (51.60%, 97/188; P < 0.05). Key manifestations included memory impairment (33.50%, 401/1,197), arthralgia (33.08%, 396/1,197), alopecia (32.25%, 386/1,197) and visual decline (31.08%, 372/1,197). Laboratory abnormalities persisted for ≥10 years in 0.33% of survivors, notably thrombocytopenia, elevated lactate dehydrogenase, and cystatin C. Compared to non-SFTS group, a significantly higher proportion of SFTS survivors had decreased white blood cell count, eosinophil percentage and mean corpuscular hemoglobin. The long-term sequelae risk exhibited distinct patterns across factors: encephalitis development was associated with significantly higher risks of memory impairment (adjusted OR=2.39) and thrombocytopenia (adjusted OR=3.36); corticosteroid usage during hospi-talization showed increased risks of arthralgia (adjusted OR=2.17) and elevated BUN (adjusted OR=3.87); while high viral load (≥1 × 106 copies/mL) exhibited significantly higher incidences of most prevalent clinical manifestations and multiple laboratory abnormalities (all P < 0.05). Conclusion SFTS survivors exhibit multisystemic sequelae, with high viral load and acute-phase neurological involvement serving as critical prognostic indicators. These findings underscore the need for long-term monitoring and targeted therapeutic strategies for SFTS.