Systematic review and meta-analysis of virome profiles and quantification of Torque teno virus load in blood of acute febrile illness patients

Acute febrile illness (AFI) is a sudden fever which can be caused by various viruses such as dengue, Zika, and chikungunya viruses. This study aimed to identify viruses present in AFI patients via metagenomic next-generation sequencing (mNGS) through meta-analysis, and to compare the prevalence and viral load of the common viruses between AFI patients and healthy blood donors in northeastern Thailand. Our meta-analysis revealed that human anelloviruses-including torque teno virus (TTV), torque teno mini virus (TTMV), and torque teno midi virus (TTMDV)-were the most prevalent viruses detected. We confirmed their presence in peripheral blood mononuclear cells from 203 AFI patients and 100 healthy blood donors using real-time PCR. TTV was the most identified anellovirus, detected in 84% of healthy donors and 61.08% of AFI patients. The mean TTV load was significantly lower in AFI patients compared to healthy donors. In AFI patients, TTV load increased in those with higher total white blood cell and neutrophil counts but decreased in those with higher lymphocyte counts. Our findings demonstrate high prevalence of anelloviruses, particularly TTV, in both AFI patients and healthy donors, and highlight the potential value of the TTV load in blood as an immune status biomarker in AFI patients.