Clinical Spectrum and Dynamics of Sequelae Following Tick-Borne Encephalitis Virus Infection: A Systematic Literature Review.

Abstract

Background: Infection with the tick-borne encephalitis virus (TBEV) can affect the nervous system and lead to significant morbidity. To summarize current knowledge of long-term outcomes following TBEV infection, we systematically reviewed the prevalence of TBEV infection sequelae after hospital discharge across different age groups and follow-up time points.

Methods: Studies of adults, children, and "all-age" populations with laboratory-confirmed TBEV infection were identified via electronic database searches. Study categorization was based on follow-up time after hospital discharge: ≤6, 7 to ≤12, or >12 months. Sequelae signs/symptoms were divided into 3 categories: neurological, neuropsychiatric, and other. Data were normalized using weighted means. Heterogeneity was estimated using a meta-analytic random-effects model.

Results: Fifteen studies were eligible for analysis (13 included only hospitalized patients). Seventy-nine unique sequelae symptoms were identified. Adults had a higher frequency of persistent symptoms than children (20.6%-100% vs 1.7%-69%). There were high levels of data heterogeneity (I ² > 90%) among all studies. Although the proportion of patients with each sequela fluctuated across time, headache was reported by ≥20% of patients at all time points. Some sequelae also varied by age group; for example, irritability was more frequent in children, while insomnia/sleep disorders were more frequent in adults. Predominant neurological symptoms included balance disorders and headache. Predominant neuropsychiatric symptoms included concentration and memory disorders.

Conclusions: Patients experience a variety of neurological, neuropsychiatric, or other sequelae symptoms following TBEV infection that vary over time and across age groups. This study highlights the need for standardized symptom categorization and follow-up time for TBE sequelae studies.