A case-control neuroimaging investigation of chronic Zika virus-infected adults

Suhnyoung Jun^1*Richard Bido-Medina²Jairo Oviedo³Isidro Miches⁴Daniel Llano⁵Luis Tusen⁶Peter Stoeter³Minelly Rodriguez⁶Sepideh Sadaghiani¹

• ¹Department of Psychology, University of Illinois Urbana-Champaign, Urbana, United States
• ²Massachusetts General Hospital Department of Psychiatry, Boston, United States
• ³Department of Radiology, Centros de Diagnostico y Medicina Avanzada y de Conferencias Medicas y Telemedicina, Santo Domingo, Dominican Republic
• ⁴Department of Surgery, Hospital Dr Salvador B Gautier, Santo Domingo, Dominican Republic
• ⁵Department of Molecular & Integrative Physiology, University of Illinois Urbana-Champaign, Urbana, United States
• ⁶Department of Neurology, Hospital Dr Salvador B Gautier, Santo Domingo, Dominican Republic

Systemic viral infections with neurotropic potential pose significant global health challenges. The Zika virus (ZIKV) is known for its pronounced neurotropism, with recent infectious clusters raising renewed public health concerns. While research has predominantly focused on congenital populations, growing evidence suggests that the mature central nervous system (CNS) is also vulnerable. However, no study has examined the long-term impact of ZIKV infection on the adult human brain. To address this gap, we studied a rare group of adult ZIKV patients presenting with both peripheral (Guillain-Barré Syndrome; GBS) and CNS-related neurological symptoms. We compared these patients at the chronic stage (5 to 12 months post-infection) to healthy controls and to patients with GBS of non-ZIKV etiology (total N=43). Structural and functional measures included cortical thickness, white matter hyperintensities, diffusion metrics, and resting-state functional connectivity. Despite the rarity of both patient populations, power analyses indicated that our sample size could detect large group differences—effect sizes deemed reasonable given the severity of neurological symptoms in the ZIKV group. Nonetheless, our multimodal analyses yielded null results, with Bayesian statistics (where applicable) providing evidence for a lack of effects. The null findings suggest that chronic ZIKV infection in adults is not associated with brain changes of large magnitude. Importantly, this study offers detailed clinical characterization of a heavily understudied group. In light of recent ZIKV outbreaks, this characterization underscores the need to monitor, study, and provide longitudinal care to adult survivors of severe ZIKV infections.