Introduction: Chikungunya virus (CHIKV) is an arthritogenic alphavirus that can frequently cause post-acute viral syndrome (PAVS), with painful symptoms as in Long COVID. Chronic Chikungunya is mainly characterized by chronic arthralgia (CA) and can persist for months and years, significantly impacting quality of life. Currently, there is no vaccine or therapy. Identifying mechanisms behind disease progression can reveal potential diagnosis and therapeutic targets to mitigate Chikungunya and other PAVS.Methods: We analyzed bulk transcriptome of PBMC obtained during acute CHIKV infection of patients that further recovered (n=11) or evolved to CA persisting for one year (n=24). Healthy controls (n=9) were also included. Total RNA extracted from PBMC was used for library preparation with TruSeq Stranded Total RNA Library Prep and sequenced with NextSeq(Illumina). DESeq2 was used to identify differentially expressed genes (DEG). RT-PCR of the selected differentially expressed genes was used to validate the results in another group of CA (n=21) and recovered (n=11) cases. Results: Blood samples were collected in a median of 1 (1-3) days after disease onset for both groups, with more females in the CA group (66% versus 36%). Seven genes (PTGER3, IKZF2, ACKR3, TMEM176B, TMEM176A, NCS1, ST8SIA1) were differentially expressed between CA and recovered (Log2FC ≥|1| and FDR ≤0.1) and further validated by RT-PCR. CA group presented higher expression of IKZF2, which codes the Helios transcription factor produced by T regulatory cells. Among the three genes downregulated in the chronic group, ACKR3 acts as a scavenger for CXCL12 and is expressed by antiviral patrolling monocytes. Expression of ACKR3 negatively correlated with viral load. In conclusion, our findings revealed potential prognosis biomarkers for chronic chikungunya. In addition, results suggested early regulation of immune response can be involved in the progression to PAVS, revealing potential targets for therapy.